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Routine blood culture is used for the detection of bloodstream infections by aerobic and anaerobic bacteria and by common pathogenic yeasts. A retrospective study was conducted in a public hospital in Maceió-AL, by collecting data of all medical records with positive blood cultures. Out of the 2,107 blood cultures performed, 17% were positive with Staphylococcus coagulase negative (51.14%), followed by Staphylococcus aureus (11.21%) and Klebsiella pneumoniae (6.32%). Gram-positive bacteria predominated among positive blood cultures, highlighting the group of Staphylococcus coagulase-negative. While Gram-negative bacteria had a higher number of species among positive blood cultures. Resumo A cultura sanguínea de rotina é usada para a detecção de infecções na corrente sanguínea por bactérias aeróbias e anaeróbias e por leveduras patogênicas comuns. Estudo retrospectivo realizado em hospital público de Maceió-AL, por meio da coleta de dados de todos os prontuários com culturas sanguíneas positivas. Das 2.107 culturas sanguíneas realizadas, 17% foram positivas com Staphylococcus coagulase negativo (51,14%), seguido por Staphylococcus aureus (11,21%) e Klebsiella pneumoniae (6,32%). As bactérias Gram-positiva predominaram entre as culturas de sangue positivas, destacando-se o grupo das Staphylococcus coagulase-negativo. Enquanto as bactérias Gram-negativas apresentaram um número maior de espécies entre as culturas de sangue positivas.

Background Protection against Plasmodium falciparum is observed in a population deficient in glucose-6-phosphate dehydrogenase (G6PD), particularly in African and Mediterranean regions. However, such protection remains unknown among G6PD-deficient individuals in Southeast Asia. Methods In this study, we assessed the invasion and maturation of P falciparum K1 in a culture of erythrocytes isolated from Thai subjects carrying Viangchan (871G > A) and Mahidol (487G > A). Results We found that the parasites lost their ability to invade hemizygous and homozygous G6PD-deficient erythrocytes of Viangchan and Mahidol variants in the second and third cycles of intraerythrocytic development. It is interesting to note that P falciparum parasites selectively grew in erythrocytes from hemi- and homozygous genotypes with normal G6PD activity. Moreover, externalization of phosphatidylserine upon P falciparum infection was significantly increased only in Viangchan hemizygous variant cells. Conclusions This study is the first to show that blockage of invasion in long-term culture and potentially enhanced removal of parasitized erythrocytes were observed for the first time in erythrocytes from Viangchan and Mahidol G6PD-deficient individuals.

Introduction The incidence of infections caused by aerobic actinomycetes is increasing. Recent changes in taxonomy and the variability in susceptibility patterns among species make necessary a proper identification and antibiotic susceptibility testing. Material and methods Fifty-three strains of aerobic actinomycetes were identified by MALDI-TOF MS using the VITEK MS Mycobacterium/Nocardia kit (bioMerieux, France) in a tertiary hospital in Spain during a six-year period. Antimicrobial susceptibility testing of the isolates was performed using the Sensititre Rapmycoi microdilution panel (Thermo Fisher Scientific, Massachusetts, USA). Results Forty strains of Nocardia spp. were identified in the study, being N. farcinica and N. cyriacigeorgica the most prevalent ones. All isolates were susceptible to linezolid and the resistance to amikacin was only observed in one isolate of Gordonia sputi. Resistance to cotrimoxazole was only found in five isolates. Conclusions Routine identification and antimicrobial susceptibility testing of aerobic actinomycetes is advisable for an efficient identification of species and effective treatment.

Bacteria are associated with the human body and colonize the gut, skin, and mucous membranes. These associations can be either symbiotic or pathogenic. In either case, bacteria derive more benefit from their host. The ability of bacteria to enter and survive within the human body can be exploited for human benefit. They can be used as a vehicle for delivering or producing bioactive molecules, such as toxins and lytic enzymes, and eventually for killing tumor cells. Clostridium and Salmonella have been shown to infect and survive within the human body, including in tumors. There is a need to develop genetic circuits, which enable bacterial cells to carry out the following activities: (i) escape the human immune system, (ii) invade tumors, (iii) multiply within the tumorous cells, (iv) produce toxins via quorum sensing at low cell densities, and (v) express suicide genes to undergo cell death or cell lysis after the tumor has been lysed. Thus, bacteria have the potential to be exploited as anticancer agents.

Due to the emergence and development of antibiotic resistance in the treatment of bacterial infections, efforts to discover new antimicrobial agents have increased. One of these antimicrobial agents is a compound produced by a large number of bacteria called bacteriocin. Bacteriocins are small ribosomal polypeptides that can exert their antibacterial effects against bacteria close to their producer strain or even non-closely-relatedstrains. Adequate knowledge of the structure and functional mechanisms of bacteriocins and their spectrum of activity, as well as knowledge of the mechanisms of possible resistance to these compounds, will lead to further development of their use as an alternative to antibiotics. Furthermore, most bacteria that live in the gastrointestinal tract (GIT) have the ability to produce bacteriocins, which spread throughout the GIT. Despite antimicrobial studies in vitro, our knowledge of bacteriocins in the GIT and the migration of these bacteriocins from the epithelial barrier is low. Hence, in this study, we reviewed general information about bacteriocins, such as classification, mechanism of action and resistance, emphasizing their presence, stability, and spectrum of activity in the GIT.

Introduction : Clinical use of mobile phones have increased exponentially. Whilst evidence of contamination is documented, a key factor when determining potential risks of contamination, is establishing the duration the organism remains viable on the device. If pathogens are found to persist for extended duration, healthcare mobile phones may become fomites for cross departmental transmission. Aim : Determine the duration pathogenic bacteria, Acinetobacter baumannii, Escherichia coli, two Pseudomonas sp. Bacillus cereus, Enterococcus faecalis susceptible and resistant to vancomycin (VSE and VRE) Staphylococcus aureus susceptible and resistant to methicillin (MSSA and MRSA), and a coagulase negative Staphylococcus (CoNs) can remain viable on a mobile phone under controlled conditions. Method : Phones were inoculated with 106 – 107 of each bacterium. The duration of viability was measured from the point the inoculum had dried and CFUs retrieved at timed intervals over 28 days. Results : The mean percentage of bacteria viable at each time point was significantly different (20mins, p=0.004, 1hour p=0.014, 6hours p = 0.006, 24hours p=0.004, 7 days p = 0.007, 14 days p = 0.003, 21 days p = 0.002- and 28-days p =0.004). Gram-positive bacteria remained viable longer than gram-negative bacteria (p=0.010). MSSA declined faster than MRSA within the first 6 hours (p=0.036). Conclusion : The extended duration of bacterial viability indicates the ability for pathogens to persist on a device and remain viable long enough to be transmitted to new areas both within the hospital and out to the community. Mobile phone decontamination should occur in combination of hand hygiene.

Objectives To explore the in vitro antimicrobial susceptibility among clinically important Gram-negative bacteria (GNB) in Taiwan. Methods From 2016 through 2018, a total of 5458 GNB isolates, including Escherichia coli (n = 1545), Klebsiella pneumoniae (n = 1255), Enterobacter species (n = 259), Pseudomonas aeruginosa (n = 1127), Acinetobacter baumannii complex (n = 368), and Stenotrophomonas maltophilia (n = 179), were collected. The susceptibility results were summarized by the breakpoints of minimum inhibitory concentration (MIC) of CLSI 2020, EUCAST 2020 (for colistin), or published articles (for ceftolozane/tazobactam). The resistance genes among multidrug-resistant (MDR) or extensively drug-resistant (XDR)-GNB were investigated by multiplex PCR. Results Significantly higher rates of non-susceptibility (NS) to ertapenem and carbapenemase production, predominantly KPC and OXA-48-like beta-lactamase, were observed in Enterobacterales isolates causing respiratory tract infection than those causing complicated urinary tract or intra-abdominal infection (12.7%/3.44% vs. 5.7%/0.76% or 7.7%/0.97%, respectively). Isolates of Enterobacter species showed higher rates of phenotypic extended-spectrum β-lactamase and NS to ertapenem than E. coli or K. pneumoniae isolates. Although moderate activity (54–83%) was observed against most potential AmpC-producing Enterobacterales isolates, ceftolozane/tazobactam exhibited poor in vitro (44.7–47.4%) activity against phenotypic AmpC Enterobacter cloacae isolates. Additionally, 251 (22.3%) P. aeruginosa isolates exhibited the carbapenem-NS phenotype, and their MDR and XDR rate was 63.3% and 33.5%, respectively. Fifteen (75%) of twenty Burkholderia cenocepacia complex isolates were inhibited by ceftolozane/tazobactam at MICs of ≤4 μg/mL. Conclusions With the increase in antibiotic resistance in Taiwan, it is imperative to periodically monitor the susceptibility profiles of clinically important GNB.

Objectives Despite excessive resistance of Helicobacter pylori to clarithromycin among Iranian population, unfortunately, clarithromycin-based therapy is still prescribed in Iran. Recent studies have shown high rates of H. pylori eradication in patients treated with levofloxacin. The main purpose of this study was to compare the effect of levofloxacin with clarithromycin on the eradication of H. pylori infection in Iranian population. Methods A comprehensive meta-analysis was done for the relevant cohort studies and clinical trials to compare the therapeutic effects of levofloxacin with clarithromycin in Iranian population. We pooled the data using odds ratio corresponding to 95% confidence intervals to find the clinical efficacy of levofloxacin versus clarithromycin to treat H. pylori infection. The heterogeneity and publication bias were also measured for the included studies. Results A total of 13 studies were included in the quantitative synthesis. Eradication rate in patients receiving levofloxacin and clarithromycin were 75% and 66.3%, respectively (OR: 1.76; 95% CI: 1.40-2.20). In addition, in the subgroup analysis, it was confirmed that cure rate is relatively higher in levofloxacin-treated cases. However, there is significant heterogeneity as well as publication bias, thus, the results need to be interpreted with caution. Conclusions We found that the success of levofloxacin treatment was significantly higher than that of clarithromycin. Therefore, it is suggested that clarithromycin-based triple therapy be replaced by levofloxacin-based triple therapy in countries with high resistance rate to clarithromycin such as Iran. Nevertheless, findings of the present study need to be approved with larger investigation on Iranian population.

BACKGROUNDNasopharyngeal carriage of pathogenic bacteria precedes invasive disease and higher rates are found in low socioeconomic-status (SES) settings. Local immune responses are important for controlling colonization, but whether SES affects these responses is currently unknown.OBJECTIVEExamining bacterial colonization and cytokine response in nasal mucosa of children from high and low SES.METHODSTwenty-five cytokines were measured in nasal fluid. qPCR was performed to determine carriage and density of Haemophilus influenzae (H. influenzae), Streptococcus pneumoniae (S. pneumoniae), Moraxella catarrhalis (M. catarrhalis) and Staphylococcus aureus (S. aureus).RESULTSThe densities of H. influenzae and S. pneumoniae were increased in low compared to the high SES (p=0.006, p=0.026), with respectively 6 and 67 times higher median densities. Densities of H. influenzae and S. pneumoniae were positively associated with levels of IL-1beta (p=0.002, p=0.008) and IL-6 (pp=0.006). After correcting for bacterial density, IL-6 levels were increased in colonized children from high compared to low SES for both H. influenzae and S. pneumoniae (both p=0.039).CONCLUSIONIncreased density of H. influenzae and S. pneumoniae was observed in low SES children, while IL-6 levels associated with colonization were reduced in these children, indicating that immune responses to bacterial colonization were altered by SES.

Fungal corneal ulcers are an uncommon, yet challenging, cause of vision loss. In the United States, geographic location appears to dictate not only the incidence of fungal ulcers, but also the fungal genera most encountered. These patterns of infection can be linked to environmental factors and individual characteristics of fungal organisms. Successful management of fungal ulcers is dependent on an early diagnosis. New diagnostic modalities like confocal microscopy and polymerase chain reaction (PCR) are being increasingly used to detect and identify infectious organisms. Several novel therapies, including crosslinking and light therapy, are currently being tested as alternatives to conventional antifungal medications. We explore the biology of Candida, Fusarium, and Aspergillus, the three most common genera of fungi causing corneal ulcers in the United States and discuss current treatment regimens for the management of fungal keratitis.

Objective The toxin-producing Klebsiella oxytoca causes antibiotic-associated haemorrhagic colitis (AAHC). The disease-relevant cytotoxins tilivalline and tilimycine produced by certain K. oxytoca isolates are encoded by the non-ribosomal peptide synthetase genes A (npsA) and B (npsB). In this study, the new LightMix® Modular kit for detection of relevant K. oxytoca sensu lato (s.l.) toxin genes was evaluated. Methods DNA was extracted on the automated EMAG® platform. Amplification was done on the Light Cycler® 480 II instrument. A total of 130 residual faecal specimens that had been collected from patients with antibiotic-associated diarrhoea were studied to determine the clinical sensitivity and specificity. Toxigenic culture served as reference method. Results With the new kit, the limit of detection was 15 CFU/mL for all targets. For the K. oxytoca s.l. specific pehX target, 65 of 130 clinical specimens were positive while toxin specific targets (npsA/npsB) were positive in 47 of 130. The npsA/npsB PCR targets showed a clinical sensitivity of 100% (95% CI of 80.5% to 100%) and a specificity of 73.5% (95% CI of 64.3% to 81.3%) with a positive predictive value of 16.5% (95% CI of 12.7% to 21.2%) and a negative predictive value of 100%. Conclusion Compared with culture, additional K. oxytoca s.l.-positive clinical specimens were detected with real-time PCR. The specificity of the toxin targets appears moderate due to the inferior sensitivity of the culture-based reference method. Since the developed assay is highly sensitive, it may be used as first-line method to improve AAHC diagnosis.

Aims To evaluate the biological activity of extracts from cultures of marine bacteria against Toxoplasma gondii and Mycobacterium tuberculosis. Methods and Results Ethyl acetate extracts obtained from seven marine bacteria were tested against T. gondii GFP-RH and M. tuberculosis H37Rv. The cytotoxicity on HFF-1 cells was measured by a microplate resazurin fluorescent approach, and the haemolytic activity was determined photometrically. The extracts from Bacillus sp. (INV FIR35 and INV FIR48) affected the tachyzoite viability. The extracts from Bacillus, Pseudoalteromonas, Streptomyces and Micromonospora exhibited effects on infection and proliferation processes of parasite. Bacillus sp. INV FIR48 extract showed an minimum inhibitory concentration value of 50 µg ml−1 against M. tuberculosis H37Rv. All the extracts exhibited relatively low toxicity to HFF-1 cells and the primary culture of erythrocytes, except Bacillus sp. INV FIR35, which decreased cell viability under 20%. Liquid chromatography coupled to mass spectrometry analysis of the most active bacterial extract Bacillus sp. INV FIR48 showed the presence of peptide metabolites related to surfactin. Conclusions The extract from culture of deep-sea Bacillus sp. INV FIR48 showed anti-T. gondii and anti-tuberculosis (TB) biological activity with low cytotoxicity. In addition, peptide metabolites were detected in the extract. Significance and Impact of the Study Toxoplasmosis and TB are among the most prevalent diseases worldwide, and the current treatment drugs exhibit side effects. This study confirm that marine bacteria are on hand sources of anti-infective natural products.

BACKGROUND/PURPOSE Klebsiella pneumoniae bacteremia-induced sepsis is a clinically important condition with a high mortality rate and various known virulence factors. However, studies on the association of these virulence factors with the occurrence of K. pneumoniae bacteremia-induced sepsis are scarce. We aimed to investigate clinical variables and virulence factors in patients with K. pneumoniae bacteremia-induced sepsis. METHODS We retrospectively reviewed the medical records of 76 patients with K. pneumoniae bacteremia between January 2012 and July 2017. Patients were divided into sepsis (n = 25) and non-sepsis (n = 51) groups. Patient background characteristics, antimicrobial regimens, and prognosis were evaluated. We assessed the distribution of virulence factors related to K. pneumoniae, such as mucoviscosity, capsular polysaccharide, and siderophores. Siderophore production levels were determined by measuring the orange halo zone on chrome azurol S agar plate assay. RESULTS There were no intergroup differences in male-to-female ratio and age. Multivariable analysis revealed that siderophore production level (p

Breast milk is a complex biological fluid. Additionally to its nutritional impact, it contains diverse bioactive elements related to early metabolic programming and molecular structures, such as microRNA related to the epigenetic signaling process. Now, we know that human milk is not sterile and contains a significant diversity of microorganisms such as bacteria (bacterioma), viruses (viroma) and fungi (mycobiome), all of which integrate the concept of the human milk microbiota. Apparently the origin of this microbiota is found in the entero-mammary circulation, as well as in the retrograde circulation of the skin of the mammary gland, although it is speculated in what percentage the microbiota of the oral cavity of the infant contributes in a significant way. From a functional point of view, it has been shown the transfer of this microbiota to the infant's digestive tract, which is related to better digestive tolerance, lower frequency and intensity of dysfunctionalities of the brain-intestine-microbiota axis, and improved immunity, among others.La leche materna es un fluido biológico complejo, ya que además de nutrir, contiene diversos elementos bioactivos relacionados con el fenómeno de programación metabólica temprana e incluso contiene estructuras moleculares relacionadas con el proceso de señalización epigenética tales como los microARN. Ahora sabemos que la leche humana no es estéril y contiene una diversidad significativa de microorganismos tales como bacterias (bacterioma), virus (viroma) y hongos (micobioma), todo lo cual integra el concepto de microbiota de leche humana. Al parecer el origen de esta microbiota se encuentra en la circulación enteromamaria, así como en la circulación retrógrada de la piel de glándula mamaria, aunque se especula en qué porcentaje la microbiota de la cavidad bucal del lactante contribuye de forma significativa. Desde el punto de vista funcional, se ha demostrado transferencia de esta microbiota hacia el tubo digestivo del lactante, lo que se relaciona con una mejor tolerancia digestiva, menor frecuencia e intensidad de disfuncionalidades del eje cerebro-intestino-microbiota, y mejora de la inmunidad, entre otras.

Now a day’s multidrug resistance phenomenon has become the main cause for concern and there has been an inadequate achievement in the development of novel antibiotics to treat the bacterial infections. Therefore, there is an unmet need to search for novel adjuvant. Vitamin C is one such promising adjuvant. The present study was aimed to elucidate the antibacterial effect of vitamin C at various temperatures (4°C, 37°C and 50°C) and pH (3, 8, and 11), against Gram-positive and Gram-negative bacteria at various concentrations (5-20 mg/ml) through agar well diffusion method. Growth inhibition of all bacterial strains by vitamin C was concentration-dependent. Vitamin C significantly inhibited the growth of Gram-positive bacteria: Bacillus licheniformis (25.3 ± 0.9 mm), Staphylococcus aureus (22.0 ± 0.6 mm), Bacillus subtilis (19.3 ± 0.3 mm) and Gram-negative bacteria: Proteus mirabilis (27.67 ± 0.882 mm), Klebsiella pneumoniae (21.33±0.9 mm), Pseudomonas aeruginosa (18.0 ± 1.5 mm) and Escherichia coli (18.3 ± 0.3 mm). The stability of vitamin C was observed at various pH values and various temperatures. Vitamin C showed significant antibacterial activity at acidic pH against all bacterial strains. Vitamin C remained the stable at different temperatures. It was concluded that vitamin C is an effective and safe antibacterial agent that can be used in the future as an adjunct treatment option to combat infections in humans. Resumo Agora, a resistência antimicrobiana de um dia em patógenos aos antibióticos tornou-se a principal causa de preocupação e houve uma realização inadequada no desenvolvimento de novos antibióticos para tratar infecções bacterianas. Portanto, há uma necessidade de pesquisar um novo adjuvante, e a vitamina C é um desses adjuvantes promissores. O objetivo do presente estudo foi elucidar o efeito antibacteriano da vitamina C em diferentes temperaturas (4 °C, 37 °C e 50 °C) e pH (3, 8 e 11), contra Gram-positivos e Gram-cepas bacterianas negativas em várias concentrações (5-20 mg / ml) através do método de difusão em ágar bem. A inibição do crescimento de todas as cepas bacterianas pela vitamina C era dependente da concentração. A vitamina C inibiu significativamente o crescimento de bactérias Gram-positivas: Bacillus licheniformis (25,3 ± 0,9 mm), Staphylococcus aureus (22,0 ± 0,6 mm), Bacillus subtilis (19,3 ± 0,3 mm) e bactérias Gram- negativas: Proteus mirabilis (27,7 ± 0,9 mm), Klebsiella pneumoniae (21,3 ± 0,9 mm), Pseudomonas aeruginosa (18,0 ± 1,5 mm) e Escherichia coli (18,3 ± 0,3 mm). A estabilidade da vitamina C foi observada em vários valores de pH e várias temperaturas. A vitamina C mostrou atividade antibacteriana significativa em pH ácido contra todas as cepas bacterianas. A estabilidade da vitamina C permaneceu nas mesmas diferentes temperaturas (4 °C, 37 °C e 50 °C). Concluímos que a vitamina C é um agente antibacteriano eficaz e seguro que pode ser usado no futuro como uma opção de tratamento auxiliar para combater infecções em humanos, pois pode apoiar o sistema imunológico diretamente.

The study was aimed to assess impact of high fat diet (HFD) and synthetic human gut microbiota (GM) combined with HFD and chow diet (CD) in inducing type-2 diabetes (T2D) using mice model. To our knowledge, this is the first study using selected human GM transplantation via culture based method coupled dietary modulation in mice for in vivo establishment of inflammation leading to T2D and gut dysbiosis. Twenty bacteria (T2D1-T2D20) from stool samples of confirmed T2D subjects were found to be morphologically different and subjected to purification on different media both aerobically and anerobically, which revealed seven bacteria more common among 20 isolates on the basis of biochemical characterization. On the basis of 16S rRNA gene sequencing, these seven isolates were identified as Bacteroides stercoris (MT152636), Lactobacillus acidophilus (MT152637), Lactobacillus salivarius (MT152638), Ruminococcus bromii (MT152639), Klebsiella aerogenes (MT152640), Bacteroides fragilis (MT152909), Clostridium botulinum (MT152910). The seven isolates were subsequently used as synthetic gut microbiome (GM) for their role in inducing T2D in mice. Inbred strains of albino mice were divided into four groups and were fed with CD, HFD, GM+HFD and GM+CD. Mice receiving HFD and GM+modified diet (CD/HFD) showed highly significant (P

Colletotrichum is one of the most economically important fungal genera, which affects a wide range of hosts, specifically tropical and subtropical crops. Thus far, there have been several records of mycovirus infection in Colletotrichum spp., primarily by viruses of the Partitiviridae family. There have also been records of infections by mycoviruses of the Chrysoviridae family. Mycoviruses are (+)ssRNA and dsRNA genome viruses, which may or may not be enveloped. To date, no mycovirus with a DNA genome has been isolated from Colletotrichum spp. Typically, mycoviruses cause latent infections, although hypo- and hypervirulence have also been reported in Colletotrichum spp. In addition to its effects on pathogenic behavior, mycovirus infection can lead to important physiological changes, such as altered morphological characteristics, reduced vegetative growth, and suppressed conidia production. Therefore, research on mycoviruses infecting phytopathogenic fungi can help develop alternative methods to chemical control, which can cause irreversible damage to humans and the environment. From an agricultural perspective, mycoviruses can contribute to sustainable agriculture as biological control agents via changes in fungal physiology, ultimately resulting in the total loss of or reduction in the virulence of these pathogens.

Aims To isolate and characterise phage which could lyse P. acnes and to formulate the phage into a delivery form for potential application in topical treatment of acne infection. Methods and Results Using standard phage isolation techniques, ten phage capable of lysing P. acnes were isolated from human skin microflora. Their genomes showed high homology to previously reported P. acnes phage. These phage were formulated into cetomacrogol cream aqueous at a concentration of 2.5x108 PFU per gram, and shown to lyse underlying P. acnes cells grown as lawn cultures. These phage formulations remained active for at least 90 days when stored at four degrees Celsius in a light protected container. Conclusions P. acnes phage formulated into cetomacrogol cream aqueous will lyse surrounding and underlying P. acnes bacteria, and are effective for at least 90 days if stored appropriately. Significance and Impact of the Study There are few reports of phage formulation into semi solid preparations for application as phage therapy. The formulation method described here could potentially be applied topically to treat human acne infections. The potential exists for this model to be extended to other phage applied to treat other bacterial skin infections.

Subversion of host cell apoptotic responses is a prominent feature of viral immune evasion strategies to prevent premature clearance of infected cells. Numerous poxviruses encode structural and functional homologs of the Bcl-2 family of proteins, and vaccinia virus harbors antiapoptotic F1L that potently inhibits the mitochondrial apoptotic checkpoint. Recently F1L has been assigned a caspase-9 inhibitory function attributed to an N-terminal α helical region of F1L spanning residues 1–15 (1) preceding the domain-swapped Bcl-2-like domains. Using a reconstituted caspase inhibition assay in yeast we found that unlike AcP35, a well characterized caspase-9 inhibitor from the insect virus Autographa californica multiple nucleopolyhedrovirus, F1L does not prevent caspase-9-mediated yeast cell death. Furthermore, we found that deletion of the F1L N-terminal region does not impede F1L antiapoptotic activity in the context of a viral infection. Solution analysis of the F1L N-terminal regions using small angle x-ray scattering indicates that the region of F1L spanning residues 1–50 located N-terminally from the Bcl-2 fold is an intrinsically unstructured region. We conclude that the N terminus of F1L is not involved in apoptosis inhibition and may act as a regulatory element in other signaling pathways in a manner reminiscent of other unstructured regulatory elements commonly found in mammalian prosurvival Bcl-2 members including Bcl-xL and Mcl-1.

BACKGROUND/PURPOSE Salmonella Panama was considered an invasive non-typhoidal Salmonella (iNTS) serovar. Comprehensive clinical, microbiological, and genomic studies on S. Panama are scarce. We aimed to characterize the clinical and microbiological characteristics of S. Panama infection. Virulence mechanism of S. Panama and other iNTS serovars were also examined. METHODS Based on data from the longitudinal surveillance system for Salmonella deployed in Taiwan since 2004, a case-control study was undertaken to evaluate clinical characteristics of S. Panama infection during an outbreak in 2015-2016. Cellular experiments were conducted to compare pathogenicity of S. Panama and other iNTS with S. Typhimurium. RESULTS Most patients (41/44, 93.2%) infected by S. Panama were

Aims To explore the in vitro ability of alpha haemolytic streptococcus (AHS) and lactobacilli (LBs), from Indigenous Australian children, to inhibit the growth of respiratory pathogens (Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis), also from Indigenous Australian children. Methods and Results The bacterial interference of 91 isolates, from Indigenous Australian children both with and without otitis media (OM) or rhinorrhoea, was investigated using agar overlay and cell-free supernatant. Promising isolates underwent whole genome sequencing to investigate upper respiratory tract tropism, antibiotic resistance and virulence. Antibiotic susceptibility was examined for ampicillin, amoxicillin +clavulanic acid and azithromycin. Differences in the strength of bacterial inferences in relation to OM was examined using a case series of three healthy and three children with OM. LBs readily inhibited the growth of pathogens. AHS were less effective, although several isolates inhibited S. pneumoniae. One L. rhamnosus had genes coding for pili to adhere to epithelial cells. We detected antibiotic resistance genes coding for antibiotic efflux pump and ribosomal protection protein. LBs were susceptible to antimicrobials in vitro. Screening for virulence detected genes encoding for two putative capsule proteins. Healthy children had AHS and LB that were more potent inhibitors of respiratory pathogens in vitro than children with OM. Conclusions L. rhamnosus from remote Indigenous Australian children are potent inhibitors of respiratory pathogens in vitro. Significance and Impact of Study Respiratory/ear disease are endemic in Indigenous Australians. There is an urgent call for more effective treatment/prevention; beneficial microbes have not been explored. L. rhamnosus investigated in this study are potent inhibitors of respiratory pathogens in vitro and require further investigation.

Naegleria fowleri, Balamuthia mandrillaris, and Acanthamoeba spp. can cause devastating brain infections in humans which almost always result in death. The symptoms of the three infections overlap, but brain inflammation and the course of the disease differ, depending on the amoeba that is responsible. Understanding the differences between these amoebae can result in the development of strategies to prevent and treat these infections. Recently, numerous scientific advancements have been made in the understanding of pathogenicity mechanisms in general, and the basic biology, epidemiology, and the human immune response towards these amoebae in particular. In this review, we combine this knowledge and aim to identify which factors can explain the differences between the lethal brain infections caused by N. fowleri, B. mandrillaris, and Acanthamoeba spp.

The composition of the gut microbiome is greatly influenced by nutrition and dietary alterations which can also induce large temporary microbial shifts. However, the molecular mechanisms that promote these changes remain to be determined. Species of the family Lactobacillaceae and Bacillus species are genetically manipulatable bacteria that are naturally found in the human gastrointestinal (GI) tract and are often considered models of beneficial microbiota. Here, we identify specific conserved molecular pathways that play a key role in host colonization by beneficial members of the microbiota. In particular, we highlight three pathways important to the success of lactic acid bacteria (LAB) in the GI tract: glycolysis and fermentation, microbial communication via membrane vesicles, and condition-dependent antibiotic production. We elaborate on how the understanding of these circuits can lead to the development of novel therapeutic approaches to combat GI tract infections.

Abstract: As the world manages the impact of a global pandemic caused by COVID-19, the discovery of new antiviral agents has become way more relevant and urgent. Viruses are submicroscopic infectious agents that replicate inside the living cells of different organisms. These viruses use nucleic acids (both DNA and RNA) for further replication and maturity inside the cells. Some of the viruses responsible for various human and plant diseases belong to the classes of Picornaviridae, Retroviridae, Orthomyxoviri-dae, Flaviviridae, Pneumoviridae, Virgaviridae, and Hepadnaviridae, and their treatment options are lim-ited or non-existent. The consistent reemergence and resistance development in the viral strains demand the discovery and development of new antiviral drugs possessing better efficacy. Bio-active compounds isolated from fungi can be the source of new compounds with enhanced potency and new mechanisms of action. Fungi are known to produce a diverse lot of secondary metabolites due to their existence in harsh and testing climates which are often inhabitable for many organisms. Because of these unique environ-ments, fungi produce a variety of secondary metabolites of different chemical classes like alkaloids, qui-nones, furanone, pyrones, benzopyranoids, xanthones, terpenes, steroids, peptides, and many acyclic com-pounds. Fungal metabolites are known to display a wide range of bioactive attributes, i.e., anticancer, antibacterial, antifungal, and anti-Alzheimer's, along with antiviral properties. In this review article, we report over 300 antiviral compounds from fungal sources during the period of 2009 to 2019. The source of these compounds is marine and endophytic fungi and they are arranged based on their antiviral action against different viral families. These compounds offer promise for their use and development as future antiviral drugs.

Recurrent aphthous stomatitis (RAS) is a common recurrent ulcerative disease of the oral mucosa which is closely related to oral microbial composition. However, the specific effect and the mechanism of smoking in RAS are unclear. In this study, 16S rRNA sequencing technology was used to compare the differences in saliva microbial community between 28 non-smoking healthy controls (NSctrl), 31 non-smoking RAS patients (NSras), and 19 smoking RAS patients (Sras). The results showed that the bacterial community diversity in patients with RAS (NSras and Sras) was lower than that of NSctrl. The microbial community in smoking-associated RAS is less diverse and distinct from that of non-smokers. The RAS groups have higher abundance of Veillonella, Rothia, and Sneathia and lower abundance of Bacteroidales, Bacteroides, Wolinella, Moryella, Pyramidobacter, and Christensenellaceae at the genera level. A significantly different abundance of Anaerovorax, Candidatus Endomicrobium, Lactococcus, Sneathia, Veillonella, and Cloacibacterium was observed between the Sras and the NSras group. Notably, there was a significant difference in many species from the genus Prevotella and Treponema between the NSras and the Sras group. Further, the relative abundance of several taxa is correlated with smoking age or frequency, including Megasphaera, Haemophilus, Leptotrichia, and Rothia at the genera level, and Prevotella melaninogenica, Prevotella salivae, Megasphaera micronuciformis, Haemophilus parainfluenzae, Alloprevotella tannerae, Actinomyces naeslundii, Lautropia mirabilis, and Capnocytophaga sputigena at the species level. Among patients with RAS, smoking aggravated the pathways of respiration and human pathogens. Our results suggest that smoking is closely related to changes in the oral microbiota, which may contribute an opposite effect to the pathogenesis of RAS. This study provides new insight and theoretical basis for the cause and pathogenesis of RAS and better prevention and treatment.

The present study was conducted to reveal the concentrations and patterns of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) in seven species of freshwater aquatic products ( procambarus clarkii, ctenopharyngodon idellus, parabramis pekinensis, hypophthalmichthys molitrix, cyprinus carpioio, aristichthys nobilis, carassius auratus ) collected from freshwater aquaculture farms around Changsha, China. And the OCPs and PCBs in the muscle tissue of the aquatic products were analyzed to assess the dietary intake risk. The mean concentrations of OCPs and PCBs varied between 6.38 - 15.90 and 3.18 - 5.12 ng g -1 wet weight, respectively. Heptachlor and δ-HCH are the main contaminants of OCPs in the tested aquatic products, which account for over 74% of the total OCPs. The PCB52 is the main contaminant of PCBs, which account for over 88% of the total PCBs. The bioaccumulation levels of OCPs and PCBs in the aquatic products depend upon the species of aquatic products. The ctenopharyngodon idellus has the highest contamination levels of OCPs while the hypophthalmichthys molitrix has the highest contamination levels of PCBs. The mean lipid content in the freshwater aquatic products varies from 6.08% to 19.8% (dry weight) and presents a significant correlation with the contents of OCPs and PCBs. The health risk of the freshwater aquatic products is assessed by the hazard ratios and hazard quotient, a carcinogenic risk is found for the consumption of freshwater aquatic products.

The human pathogen Clostridioides difficile colonises the gastrointestinal tract following antibiotic exposure, which causes perturbations in the beneficial microbiome. An unusual feature of C. difficile among the gut microbiota is its ability to produce high concentrations of the antimicrobial compound para-cresol, which selectively targets Gram-negative bacteria. Production of p-cresol occurs either by: (a) tyrosine fermentation via the intermediate para-hydroxyphenylacetate (p-HPA), or (b) direct turnover of exogenous p-HPA in the human gut. p-HPA is decarboxylated to produce p-cresol, by the action of HpdBCA decarboxylase encoded by the hpdBCA operon. HpdBCA decarboxylase production is induced at the transcriptional level by elevated p-HPA, which causes elevated p-cresol production, that significantly reduces microbiome diversity and richness. This deleterious effect of p-cresol on the beneficial gut microbiome is advantageous for C. difficile pathogenesis and infection relapse. Inhibiting this pathway would provide a highly specific therapeutic.

Background Pyelonephritis is one of the most serious bacterial illnesses during childhood. Gram-negative organisms account for up to 90% of the cases. Gram-positive bacteria are uncommon causes of urinary tract infections, and only a few cases caused by Facklamia hominis have been reported in the literature. Case presentation A five-year-old girl with tracheostomy and gastrostomy and past medical history of congenital lymphangioma presented with a two-week history of with intermittent fever, frequent urination, and vesical tenesmus. Diagnosis of pyelonephritis was made. Urine culture reported colonies with alpha-hemolysis in blood agar at 48-h of incubation and Facklamia hominis was identified by MALDI-TOF. The patient was successfully treated with gentamicin. Conclusions This is the first reported case of pyelonephritis by Facklamia hominis in a child, and the second involving infection in a pediatric patient. Although this pathogen is uncommon, current treatment of F. hominis is a challenge for physicians. This case illustrates the requirement to standardize identification and treatment of care to avoid treatment failure and antimicrobial resistance.

Background The emergence of concurrent levofloxacin- and trimethoprim/sulfamethoxazole (TMP/SMX)-resistant Stenotrophomonas maltophilia (LTSRSM) in Taiwan is becoming a serious problem, but clinical data analysis on this has not been reported. Methods A matched case-control-control study was conducted to investigate risk factors for LTSRSM occurrence in hospitalized patients. For patients with LTSRSM infection/colonization (the case group), two matched control groups were used: control group A with levofloxacin- and TMP/SMX-susceptible S. maltophilia (LTSSSM) and control group B without S. maltophilia. Besides, tigecycline, ceftazidime, cefepime, ciprofloxacin, gentamicin, amikacin, and colistin susceptibilities in collected LTSRSM and levofloxacin- and TMP/SMX-susceptible S. maltophilia (LTSSSM) isolates were compared. Results From January 2014 to June 2016, 129 LTSRSM from cultured 1213 S. maltophilia isolates (10.6%) were identified. A total of 107 LTSRSM infected patients paired with 107 LTSSSM-, and 107 non-S. maltophilia-infected ones were included. When compared with control group A, previous fluoroquinolone and TMP/SMX use was found to be independently associated with LTSRSM occurrence. When compared with control group B, mechanical ventilation, cerebrovascular disease, and previous fluoroquinolone use were risk factors for LTSRSM occurrence. Eighty-five LTSRSM and 85 LTSSSM isolates were compared for antibiotic susceptibilities; the resistance rates and minimum inhibitory concentrations of tigecycline and ceftazidime were significantly higher for LTSRSM than for LTSSSM isolates. Conclusion The emergence of LTSRSM showing cross resistance to tigecycline and ceftazidime would further limit current therapeutic options. Cautious fluoroquinolone and TMP/SMX use may be helpful to limit such high-level resistant strains of S. maltophilia occurrence.

Introduction Carbapenems are frequently used in the treatment of multidrug-resistant infections caused by Klebsiella pneumoniae. The aim of the study is to definition and incidence of transferable carbapenemase genes of carbapenem resistant K. pneumoniae (CRKP) and to determine clonal relatedness of these strains in tertiary care hospital in Turkey. Methods Identification of all 100 K. pneumoniae isolates and low sensitivity to any of the carbapenem group antibiotics were determined by Vitek-2 (BioMerieux, France). The frequency of carbapenemase genes (blaOXA-48, blaNDM, blaKPC, blaVIM, blaIMP) and extended spectrum beta-lactamase (ESBL) genes (blaCTX-M, blaSHV, blaTEM) which frequently detected in Turkey, have been investigated by multiplex polymerase chain reaction (PCR). Clonal relatedness was determined using Pulsed-field gel electrophoresis(PFGE). Results Ninety five isolates carried at least one of the carbapenemase genes (81.05% blaOXA-48, 38.9% blaNDM, 9.47% blaKPC,1.05% blaVIM). One isolate was carried the blaOXA-48+KPC and the two isolates were carried the blaKPC+NDM. PFGE demonstrated the presence of 24 pulse types and 63.09% of the isolates were in four main pulse types. Conclusions This study demonstrated the incidence of blaNDM is beginning to reach endemic levels, in addition to blaOXA-48 found endemic in Turkey. To our knowledge, this is the first report of the co-production of these two genes (blaKPC + NDM and blaOXA-48 + KPC) in CRKP isolates.

Extraintestinal pathogenic Escherichia coli (ExPEC) include several serotypes that have been associated with colibacillosis in poultry and with urinary tract infections (UTIs) and newborn meningitis in humans. In this study, 57 antimicrobial-resistant E. coli from apparently healthy broiler chickens were characterized for their health and safety risks. These isolates belonged to 12 serotypes, and isolates of the same serotype were clonal based on single nucleotide variant analysis. Most of the isolates harbored plasmids; IncC and IncFIA were frequently detected. The majority of the resistant isolates harbored plasmid-mediated resistance genes, including aph(3″)-Ib, aph(6)-Id, blaCMY-2, floR, sul1, sul2, tet(A), and tet(B), in agreement with their resistant phenotypes. The class 1 integron was detected in all E. coli serotypes except O124:H25 and O7:H6. Of the 57 broiler E. coli isolates, 27 were avian pathogenic, among which 18 were also uropathogenic E. coli and the remainder were other ExPEC. The two isolates of serotype O161:H4 (ST117) were genetically related to the control avian pathogenic strains and a clinical isolate associated with UTIs. A strain of serotype O159:H45 (ST101) also was closely related to a UTI isolate. The detected virulence factors included adhesins, invasins, siderophores, type III secretion systems, and toxins in combination with other virulence determinants. A broiler isolate of serotype O7:H18 (ST38) carried the ibeA gene encoding a protein involved in invasion of brain endothelium on a 102-kbp genetic island. This isolate moderately adhered and invaded Caco-2 cells and induced mortality (42.5%) in a day-old-chick infection model. The results of this study suggest that multiple antimicrobial-resistant E. coli isolates recovered from apparent healthy broilers can be pathogenic and act as reservoirs for antimicrobial resistance genes, highlighting the necessity of their assessment in a "One-Heath" context.

Purpose Nontuberculous mycobacteria (NTM) infection is an important issue after lung transplantation. However, a large-scale epidemiological study on this issue in Korea is lacking. We aimed to evaluate the epidemiology of NTM infection after lung transplant surgery in Korea. Methods Between October 2012 and December 2018, we retrospectively evaluated lung transplant recipients in a referral hospital in South Korea. A total of 215 recipients were enrolled. The median age at transplantation was 56 years (range, 17–75), and 62% were men. Bronchoscopy was performed according to the surveillance protocol and clinical indications. A diagnosis of NTM infection was defined as a positive NTM culture from a bronchial washing, bronchoalveolar lavage sample, or two separate sputum samples. We determined NTM pulmonary disease (NTM-PD) according to the American Thoracic Society/Infectious Disease Society of America 2007 guidelines. The Kaplan–Meier method and log-rank test were used for conditional survival analysis in patients with follow-up of ≥12 months. Results Fourteen patients (6.5%) were diagnosed with NTM infection at a median of 11.8 months (range, 0.3–51.4) after transplantation. Nine patients (4.2%) were diagnosed with NTM-PD, and the incidence rate was 1980/100,000 person-years. Mycobacterium abscessus was the most common species causing NTM-PD (66%), followed by M. avium complex (33%). The presence of NTM infection did not influence all-cause mortality among those who underwent follow-up for ≥12 months (N = 133, log-rank P = 0.816). Conclusion The incidence of NTM-PD was considerably high among lung-transplant recipients. M. abscessus was the most common causative species of NTM-PD after lung transplantation.

Background Ralstonia pickettii is an opportunistic waterborne microbe which can survive in many kinds of solutions. Contamination of these solutions may result as outbreaks, which can be mortal for immuncompromised patients. Herein we report an outbreak of R. pickettii related to contaminated saline infusion in our center. Methods This study was conducted in Ankara Pediatric City Hospital. An outbreak occured in Pediatric Hematology and Oncology Unit between August 28, 2019 and September 13, 2019. When the outbreak occured, infection control team began an investigation. Environmental samples were collected in order to find the source of the outbreak. Results A total of 11 patients with catheter related blood stream infection caused by R. pickettii who were diagnosed with leukemia were affected. None of the patients infected with R. pickettii died during the outbreak. A total of seventy environmental samples were cultured with the purpose of finding the source of outbreak. R. pickettii grew in normal saline solution culture and all isolates had the same clone of R. pickettii. The outbreak lasted two weeks and was controlled by stopping the usage and sending back the saline solutions belonging to the same manufacturing batch. Conclusions We reported an outbreak of R. pickettii BSIs in highly immunocompromised patients due to contaminated intravascular solution, which was rapidly controlled by infection control measures. Vigilant surveillance by hospital infection control teams and prompt investigation to identify the source of nosocomial infections are crucial to stop an outbreak.

A total of 244 Candida albicans isolates recovered from vulvovaginal candidiasis (VVC) patients in Suzhou, Eastern China, were investigated. According to CLSI documents M27-A4 and M59-3ed/M60-2ed, the MIC geometric means of nine antifungals in increasing order were micafungin (0.048 mg/L), anidulafungin (0.132 mg/L), caspofungin (0.19 mg/L), itraconazole (0.23 mg/L), posaconazole (0.25 mg/L), voriconazole (0.28 mg/L), 5-flucytosine (0.44 mg/L), amphotericin B (0.49 mg/L) and fluconazole (2.01 mg/L) respectively. Of note, 6.5% (16/244) C. albicans isolates showed resistance mainly to anidulafungin (mono-echinocandin resistance), while voriconazole had the lowest susceptibility rate of 34.8% (85/244), followed by fluconazole 59.4% (145/244), respectively. All isolates were genotyped by allelic combination of 3 microsatellite markers (CEF3, CAIII and LOC4). A total of 129 different allelic genotypes were identified, in which seven different clades were recognized with a discriminatory power of 0.96. Genotypes A-D were present in 35% of the isolates. In conclusion, decrease in antifungal drug susceptibility to C. albicans isolates from VVC is alarming. Our findings revealed the genetic diversity of C. albicans isolates among VVC patients and provided insights into the molecular epidemiology of Candida infections in China.

We observed high rates of bloodstream infections (BSIs) following fecal microbiota transplantation (FMT) for graft-versus-host-disease (33 events in 22 patients). To trace the BSIs' origin, we applied a metagenomic bioinformatic pipeline screening donor and recipient stool samples for bacteremia-causing strains in 13 cases. Offending strains were not detected in FMT donations. Enterococcus faecium, Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii could be detected in stool samples before emerging in the blood. In this largest report of BSIs post-FMT, we present an approach that may be applicable for evaluating BSI origin following microbiota-based interventions. Our findings support FMT safety in immunocompromised patients but do not rule out FMT as an inducer of bacterial translocation.

Streptococcus uberis is a common cause of mastitis. The pathogenicity among different strains of S. uberis and the resultant host immune responses remain to be elucidated. Herein, we document immune responses among 3 strains of S. uberis, and preliminary explore whether and how intestinal immunity play a role in host anti-infection processes. Mice have been proved to be effective experimental animals for bovine mastitis, so utilizing a mouse intramammary infection model, we assay immune responses and gut flora changes of 3 S. uberis strains by histopathologic examination, RT-PCR, Western blot and 16s rDNA sequencing. We find that the immune responses among the 3 sequence type (ST) S. uberis strains may be linked to the hasA/B and lbp virulence genes, and the beta diversity of the intestinal may be independent of the ST type of S. uberis. Twenty phyla and 30 genera of intestinal flora are identified, Verrucomicrobia and Akkermansia being the most prominent phylum and genus respectively. These bacteria have strong anti-inflammatory and protective effects against S. uberis challenge. These datas provide a foundation for further studies to elucidate gut flora function and exploration of therapeutic targets for mastitis. This article is protected by copyright. All rights reserved.

Diseases caused by harmful microorganisms pose a serious threat to human health. Safe and environment-friendly disinfectants are, therefore, essential in preventing and controlling such pathogens. This study aimed to investigate the antimicrobial activity and mechanism of a novel hydrogen peroxide and silver (H 2 O 2 -Ag + ) complex (HSC) in combatting Staphylococcus aureus ATCC 29213, Escherichia coli O157:H7 NCTC 12900 and Salmonella typhimurium SL 1344. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values against S. aureus were found to be 0.014 % H 2 O 2 -3.125 mg/L Ag + , while 0.028 % H 2 O 2 -6.25 mg/L Ag + for both E. coli and S. typhimurium . Results of the growth curve assay and time-kill trial suggest that the HSC could inhibit the growth of the tested bacteria, as 99.9 % of viable cells were killed following treatment at the 1 MIC for 3 h. Compared with Oxytech D10 disinfectant (0.25 % H 2 O 2 -5 mg/L Ag + ), the HSC exhibited better antibacterial efficacy at a lower concentration (0.045 % H 2 O 2 -10 mg/L Ag + ). The mechanism of antibacterial action of HSC was found including the disruption of the bacterial cell membrane, followed by entry into the bacteria cell to reduce intracellular adenosine triphosphate (ATP) concentration, and inhibit the activity of antioxidases, superoxide dismutase (SOD) and catalase (CAT). The enhanced bactericidal effect of hydrogen peroxide combined with silver indicates a potential for its application in environmental disinfection, particularly in the food industry.

When infected by Helicobacter pylori, it often causes gastritis, gastric ulcer, or gastric cancer. Antibiotics are used to treat H. pylori infection, as they inhibit or kill H. pylori often ex-tending to reduce the incidences of gastric adenoma and cancer. However, H. pylori has developed drug resistance to many clinically used antibiotics over the years, thereby providing no warranty of successful treatment whenever H. pylori infection befalls. We report here that fucoidan from Sargassumhemiphyllum can effectively reduce infection of H. pylori without development of drug resistance. Fucoidan demonstrated a strong anti-inflammation activity in RAW264.7 cell model. Using AGS cell model, fucoidan decreased H. pylori adhesion to host cells and thus reduced its infection rate, especially in post-treatment where the infection rate was reduced to 40%. Mechanistically, fucoidan intervenes the proper functions of adhesion molecules BabA and AlpA of H. pylori. Moreover, fucoidan is able to significantly lower the total count of H. pylori and the levels of IL-6 and TNF-α in vivo. Added together, these convergent results suggest that fucoidan is an effective agent in a position to protect stomach from H. pylori infection by reducing its total count and induced inflammation.

The transmission of certain bacteria from the mother's gut to the infant's gut via breast milk (BM) is critical for offspring's immune system development. Dysbiosis of the BM microbiota can be caused by a variety of reasons, which can be influenced by probiotics delivered via the enteromammary route. The goal of this study was to investigate the bacterium that can be transmitted from mother to infant's intestine during various lactation periods in 19 mother-child dyads. Bacterial transmission is most common during the colostrum phase when bacteria with certain amplicon sequence variants (ASVs) enter the newborn intestine and inhabit it permanently. We have established that anaerobic gut-associated bacteria, such as Faecalibacterium, Blautia and Lachnoclostridium, transfer from the mother to the infant's gut with lactation dependence using the idea of weighted transfer ratios. Streptococcus salivarius, Bifidobacterium longum, and Lactobacillus gasseri were transferred from the maternal gut to the BM, as well as from the BM to the newborn gut, dependent on different ASVs. These findings suggest that isolating key microorganisms from breast milk could be utilized to modify the microbiota of BM or newborns by giving the mother a probiotic or adding it to artificial milk to promote neonatal health.

Multidrug-resistant (MDR) Staphylococcus aureus biofilms have emerged as a serious threat to human health. Recently, the development of antibiotic replacement therapy has gained much attention due to the potential application of bacteriocin. The present study sought to evaluate the antibacterial effect of bacteriocin XJS01 against MDR S. aureus, a previously reported bacteriocin against S. aureus strain 2612:1606BL1486 (S. aureus_26, an MDR strain demonstrated here), and its potential application as an antibiofilm agent. The minimum bactericide concentration of XJS01 against MDR S. aureus_26 was 33.18 μg/mL. XJS01 exhibited excellent storage stability and resistance against acid and reduced the density of established MDR S. aureus_26 biofilm. The hemolytic and HEK293T cytotoxicity activities of XJS01 and the histological analyses in mice confirmed its safety. Moreover, XJS01 effectively disrupted the MDR S. aureus_26 biofilm established on the skin wound surface and reduced the biofilm-isolated bacteria, thereby decreasing the release of pro-inflammatory cytokines and the proliferation of alternatively activated macrophages. Compared to mupirocin, XJS01 exhibited an excellent therapeutic effect on mice skin wounds, confirming it to be a potential alternative to antibiotics.

Healthcare associated infections due to carbapenem-resistant Klebsiella pneumoniae (CRKP) are a major concern in Portuguese hospitals. Whole genome sequencing (WGS) can improve infection control, but this practice is not routinely used by hospital clinical laboratories in Portugal. We simulated the investigation of a CRKP outbreak based on WGS, with the aim of determining, in the minimum possible time, genetic relatedness between CRKP clinical and environmental isolates.Ten CRKP clinical isolates routinely obtained in the hospital laboratory were used. Forty environmental samples - from sinks and sink drains of ward rooms - were collected. Environmental samples were plated on selective media and presumptive CRKP colonies were isolated. Total DNA was extracted from all putative CRKP isolates and sequenced. Clonal relatedness was determined by multi-locus sequence typing and core genome single nucleotide polymorphism analysis; the presence of carbapenemase genes was evaluated.Clinical isolates were characterized in 48 hours: eight strains were confirmed as CRKP, of which six were of ST13 and carried blaKPC-3. Environmental samples results were obtained in six days: eight CRKP were isolated from which five were of ST13 and carried blaKPC-3. Clinical and environmental ST13 isolates were highly related: ten (of 11) isolates differed from each other in0.001% of 2 172 367 core nucleotides.WGS can be used as a high-resolution effective tool to investigate healthcare associated infections and track routes of dissemination in real-time.In Portugal, routine use of WGS to improve infection control could thrive through collaborative initiatives between hospitals and research institutes.Introdução: As infeções associadas aos cuidados de saúde por Klebsiella pneumoniae resistente aos carbapenemos (CRKP) são uma preocupação nos hospitais portugueses. A sequenciação total do genoma [whole genome sequencing (WGS)] pode ajudar no controlo de infecção, mas esta prática não é comummente utilizada nos laboratórios clínicos hospitalares em Portugal. O objetivo deste estudo foi simular a investigação de um surto causado por CRKP, utilizando WGS. Pretendia-se testar a utilização desta técnica e determinar, no menor tempo possível, relações genéticas entre estirpes. Material e Métodos: Foram analisados dez isolados clínicos de CRKP. Foram obtidas quarenta amostras ambientais que foram inoculadas em meio seletivo para isolamento de colónias sugestivas de CRKP e depois sequenciado o DNA total dos isolados presumptivamente identificados como CRKP A relação clonal entre as estirpes foi determinada por multi-locus sequence typing e análise de single nucleotide polymorphisms no genoma core. Foi determinada a presença de genes de carbapenemases. Resultados: Os isolados clínicos foram caraterizados em 48 horas: oito isolados foram confirmados como CRKP. A maioria pertencia ao ST13 (n = 6) e possuía o gene blaKPC-3. As amostras ambientais foram caraterizadas em seis dias: foram isoladas oito CRKP, das quais cinco eram ST13 e continham o gene blaKPC-3. Os isolados ST13 clínicos e ambientais eram muito semelhantes entre si: dez dos 11 isolados diferiam entre si em menos de 0,001% dos 2 172 367 nucleótidos core analisados. Discussão: A sequenciação total do genoma pode ser usada como uma ferramenta útil para investigar infecções nosocomiais e rastrear cadeias de disseminação em tempo real. Conclusão: Em Portugal, o uso desta técnica em controlo de infecção pode ser implementado através de colaborações entre hospitais e institutos de investigação.

To treat infections caused by Candida albicans, azoles, polyenes, and echinocandins are used. However, resistance occurs against all three, so there is an urgent need for new antifungal drugs with a novel mode of action. Recently, it became clear that central metabolism plays an important role in the virulence of C. albicans. Glycolysis is, for example, upregulated during virulence conditions, whereas the glyoxylate cycle is important upon phagocytosis by host immune cells. These findings indicate that C. albicans adapts its metabolism to the environment for maximal virulence. In this review, we provide an overview of the potency of different central metabolic pathways and their key enzymes as potential antifungal drug targets.

MSI-78A (Pexiganan A) is one of the few antimicrobial peptides (AMPs) able to kill Helicobacter pylori, a pathogenic bacterium that colonizes the gastric mucosa of half of the world's population. Antibiotics fail in 20–40% of H. pylori-infected patients, reinforcing the need for alternative treatments. Herein, a bioengineered approach was developed. MSI-78A with a C-terminal cysteine was grafted onto chitosan microspheres (AMP-ChMic) by thiol-maleimide (Michael-addition) chemistry using a long heterobifunctional spacer (NHS-PEG113-MAL). Microspheres with ∼4 µm diameter (near H. pylori length) and stable at low pH were produced by spray drying using a chitosan solution with an incomplete genipin crosslinking. A 3 × 10−5 µg AMP/microsphere grafting was estimated/confirmed by UV/Vis and FTIR spectroscopies. AMP-ChMic were bactericidal against H. pylori J99 (highly pathogenic human strain) at lower concentrations than the free peptide (∼277 µg grafted MSI-78A-SH/mL vs 512 µg free MSI-78A-SH/mL), even after pre-incubation in simulated gastric conditions with pepsin. AMP-ChMic killed H. pylori by membrane destabilization and cytoplasm release in a ratio of ∼10 bacteria/microsphere. This can be attributed to H. pylori attraction to chitosan, facilitating the interaction of grafted AMP with bacterium membrane. Overall, it was demonstrated that the peptide-microsphere conjugation chemistry did not compromise the MSI-78A antimicrobial activity, instead it boosted its bactericidal performance against H. pylori. Statement of significance Half of the world's population is infected with Helicobacter pylori, a gastric bacterium that is responsible for 90% of non-cardia gastric cancers. Therefore, H. pylori eradication is now advocated in all infected individuals. However, available antibiotic therapies fail in up to 40% patients. Antimicrobial peptides (AMPs) are appealing alternatives to antibiotics, but their high susceptibility in vivo limits their clinical translation. AMP immobilization onto biomaterials surface will overcome this problem. Herein, we demonstrate that immobilization of MSI-78A (one of the few AMPs with activity against H. pylori) onto chitosan microspheres (AMP-ChMic) enhances its anti-H. pylori activity even at acidic pH (gastric settings). These results highlight the strong potential of AMP-ChMic as an antibiotic alternative for H. pylori eradication.

Summary Intestinal flora provides an important contribution to the development of pulmonary tuberculosis (PTB). We performed a cross‐sectional study in 52 healthy controls (HCs) and 83 patients with untreated active PTB to assess the differences in their microbiomic and metabolic profiles in faeces via V3‐V4 16S rRNA gene sequencing and gas chromatography–mass spectrometry. Patients with PTB had considerable reductions in phylogenetic alpha diversity and the production of short‐chain fatty acids, dysbiosis of the intestinal flora and alterations in the faecal metabolomics composition compared with HCs. Significant alterations in faecal metabolites were associated with changes in the relative abundance of specific genera. Our study describes the imbalance of the gut microbiota and altered faecal metabolomics profiles in patients with PTB; the results indicate that the gut microbiota and faecal metabolomic profiles can be used as potential preventive and therapeutic targets for PTB., The imbalance of the gut microbiota and altered faecal metabolomics profiles in patients with PTB;Mtb infection decreased the production of SCFAs in faeces.

Background Prevalence of extended-spectrum beta-lactamase-producing-Enterobacteriaceae (ESBL-E) has risen in patients with urinary tract infections. The objective of this study was to determine explore the risk factors of ESBL-E infection in hospitalized patients and establish a predictive model. Methods This retrospective study included all patients with an Enterobacteriaceae-positive urine sample at the first affiliated hospital of Jinan university from January 2018 to December 2019. Antimicrobial susceptibility patterns of ESBL-E were analyzed, and multivariate analysis of related factors was performed. From these, a nomogram was established to predict the possibility of ESBL-E infection. Simultaneously, susceptibility testing of a broad array of carbapenem antibiotics was performed on ESBL-E cultures to explore possible alternative treatment options. Results Of the total 874 patients with urinary tract infections (UTIs), 272 (31.1%) were ESBL-E positive. In the predictive analysis, five variables were identified as independent risk factors for ESBL-E infection: male gender (OR = 1.607, 95% CI 1.066–2.416), older age (OR = 4.100, 95% CI 1.678–12.343), a hospital stay in preceding 3 months (OR = 1.872, 95% CI 1.141–3.067), invasive urological procedure (OR = 1.810, 95% CI 1.197–2.729), and antibiotic use within the previous 3 months (OR = 1.833, 95% CI 1.055–3.188). In multivariate analysis, the data set was divided into a training set of 611 patients and a validation set of 263 patients The model developed to predict ESBL-E infection was effective, with the AuROC of 0.650 (95% CI 0.577–0.725). Among the antibiotics tested, several showed very high effectiveness against ESBL-E: amikacin (85.7%), carbapenems (83.8%), tigecycline (97.1%) and polymyxin (98.2%). Conclusions The nomogram is useful for estimating a UTI patient’s likelihood of infection with ESBL-E. It could improve clinical decision making and enable more efficient empirical treatment. Empirical treatment may be informed by the results of the antibiotic susceptibility testing.

Antibiotic resistance is a health and socioeconomic crisis recognized as a serious threat affecting humans worldwide. Overuse of antibiotics enhances the spread of multidrug-resistant bacteria, causing drug-resistant infections which can be difficult to treat. This resistance, mostly of the acquired type, is thus a major clinical issue. Acquired resistance can occur by horizontal transfer of genes between bacteria (community settings), by vertical transmission that can occur between mother and her offspring at birth and during lactation, or spontaneously due to antibiotic exposure. While there have been multiple studies about the horizontal transfer of antibiotic-resistance genes, not many studies have been conducted to study their vertical transmission. Vertical transmission is of importance as the early bacterial colonization of infants has an impact on their health and immune programming throughout life. This review discusses some possible mechanisms of mother-to-infant transmission of antibiotics and antibiotic-resistant strains and addresses the knowledge gaps for further studies.

Mitogen-activated protein kinase kinase kinase 4 (MAP3K4) is a multifunctional mediator of the conserved MAPK signaling pathway that plays essential roles in the regulation of immune responses in mammals. However, the function of teleost MAP3K4s in innate immunity, especially in the intestinal immune system, is still poorly understood. In the current study, we identified a fish MAP3K4 homolog (CiMAP3K4) in Ctenopharyngodon idella as well as its immune function in intestine following bacterial infection in vivo and in vitro. The open reading frame (ORF) of CiMAP3K4 encodes putative peptide of 1544 amino acids containing a predicted serine/threonine protein kinase (S_TKc) domain with high identity with other fish MAP3K4s. Phylogenetic analysis revealed the CiMAP3K4 belonged to the fish cluster and showed the closest relationship to Pimephales promelas. Quantitative real-time PCR (qRT-PCR) analysis revealed that CiMAP3K4 transcripts were widely distributed in all tested tissues, especially with high expression in the muscle and intestine of healthy grass carp. In vitro, CiMAP3K4 gene expression was upregulated by bacterial PAMPs (lipolysaccharide (LPS), peptidoglycan (PGN), L-Ala-γ-D-Glu-meso-diaminopimelic acid (Tri-DAP) and muramyl dipeptide (MDP)) and pathogens (Aeromonas hydrophila and Aeromonas veronii) in primary intestinal cells. In vivo, the mRNA expression levels of CiMAP3K4 in the intestine were significantly induced by bacterial MDP challenge in a time-dependent manner; however, this effect could be inhibited by the bioactive dipeptides β-alanyl- l -histidine (carnosine) and alanyl-glutamine (Ala-Gln). Moreover, CiMAP3K4 was located primarily in the cytoplasm, and its overexpression increased the transcriptional activity of AP-1 in HEK293T cells. Collectively, these results suggested that CiMAP3K4 might play an important role in the intestinal immune response to bacterial infections, which paves the way for a better understanding of the intestinal immune system of grass carp.

Objectives: The incidence of healthy individuals carrying multidrug resistant Enterobacteriaceae, including extended-spectrum β-lactamase producing Enterobacteriaceae (ESBL-E), especially extended-...