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As next-generation pathogen detection methods, CRISPR-Cas-based detection methods can perform single-nucleotide polymorphism (SNP) level detection with high sensitivity and good specificity. They do not require any particular equipment, which opens up new possibilities for the accurate detection and identification of Bacillus anthracis. In this study, we developed a complete detection system for B. anthracis based on Cas12a. We used two chromosomally located SNP targets and two plasmid targets to identify B. anthracis with high accuracy. The CR5 target is completely new. The entire detection process can be completed within 90 min without electrical power and with single-copy level sensitivity. We also developed an unaided-eye visualization system based on G4-DNAzyme for use with our CRISPR-Cas12a detection system. This visualization system has good prospects for deployment in field-based point-of-care detection. We used the antisense nucleic acid CatG4R as the detection probe, which showed stronger resistance to interference from components of the solution. CatG4R can also be designed as an RNA molecule for adaptation to Cas13a detection, thereby broadening the scope of the detection system.

We highlight the need to include an analysis of the B-1 B cell subset to complement the characterization of the cell-mediated immune response to the Mycobacterium tuberculosis Beijing lineage. The literature describes the B-1 cell repertoire’s involvement in the cell-mediated response within granulomas, which is different from the classic antibody response B cells are generally associated with. Specifically, the B-1 B cell subset migrates from other compartments along with other cells to the infection site. We provide details to complement the reported results from Cerezo-Cortes et al.

Serum resistance is a poorly understood but common trait of some systemic disease pathogenic strains of bacteria. In this study, we analysed the role Escherichia coli type three secretion system 2 (ETT2) of avian pathogenic Escherichia coli (APEC) in serum resistance by bacteria survival number in serum culture, mRNA Seq and Tandem Mass Tag™ (TMT™) detection, lipopolysaccharide (LPS) extraction, and biofilm formation detection. We found that the ETT2 gene cluster deletion strain (ΔETT2) is more resistant to the killing effect of serum than wild type APEC40. The analysis of ΔETT2 compared to APEC40 in the transcriptomics and proteomics data showed that ETT2 has a negative effect in the ATP-binding cassette (ABC) translator system and quorum sensing system and a positive effect in purine metabolism. ETT2 may affect the LPS, biofilm, flagella, and fimbriae which may affect the serum resistance. These results could lead to effective strategies for managing the infection of APEC. The mRNA Seq data of this study are available in the Sequence Read Archive of the National Center for Biotechnology Information under the BioProject PRJNA757182, and proteomic raw data have been deposited under the accession number IPX0003420000 at iProX.

Microorganisms mainly exist in the form of biofilm in nature. Biofilm can contaminate food and drinking water system, as well as cause chronic wound infections, thereby posing a potential threat to public health safety. In the last two decades, researchers have made efforts to investigate the genetic contributors control different stages of biofilm development (adherence, initiation, maturation, and dispersal). As an opportunistic pathogen, C. albicans causes severe superficial or systemic infections with high morbidity and mortality under conditions of immune dysfunction. It has been reported that 80% of C. albicans infections are directly or indirectly associated with biofilm formation on host or abiotic surfaces including indwelling medical devices, resulting in high morbidity and mortality. Significantly, the outcome of C. albicans biofilm development includes enhanced invasion, exacerbated inflammatory responses and intrinsic resistance to antimicrobial chemotherapy. Thus, this review aimed at providing a comprehensive overview of the regulatory network controls microbial biofilm development, with C. albicans as a representative, served as reference for therapeutic targets.

In 2021, three encephalitis cases due to the Borna disease virus 1 (BoDV-1) were diagnosed in the north and east of Germany. The patients were from the states of Thuringia, Saxony-Anhalt, and Lower Saxony. All were residents of known endemic areas for animal Borna disease but without prior diagnosed human cases. Except for one recently detected case in the state of Brandenburg, all >30 notified cases had occurred in, or were linked to, the southern state of Bavaria. Of the three detected cases described here, two infections were acute, while one infection was diagnosed retrospectively from archived brain autopsy tissue samples. One of the acute cases survived, but is permanently disabled. The cases were diagnosed by various techniques (serology, molecular assays, and immunohistology) following a validated testing scheme and adhering to a proposed case definition. Two cases were classified as confirmed BoDV-1 encephalitis, while one case was a probable infection with positive serology and typical brain magnetic resonance imaging, but without molecular confirmation. Of the three cases, one full virus genome sequence could be recovered. Our report highlights the need for awareness of a BoDV-1 etiology in cryptic encephalitis cases in all areas with known animal Borna disease endemicity in Europe, including virus-endemic regions in Austria, Liechtenstein, and Switzerland. BoDV-1 should be actively tested for in acute encephalitis cases with residence or rural exposure history in known Borna disease-endemic areas.

Lassa fever (LF) is a deadly viral hemorrhagic disease that is endemic to West Africa. The causative agent of LF is Lassa virus (LASV), which causes approximately 300,000 infections and 5,000 deaths annually. There are currently no approved therapeutics or FDA-approved vaccines against LASV. The high genetic variability between LASV strains and immune evasion mediated by the virus complicate the development of effective therapeutics and vaccines. Here, we aim to provide a comprehensive review of the basic biology of LASV and its mechanisms of disease pathogenesis and virulence in various animal models, as well as an update on prospective vaccines, therapeutics, and diagnostics for LF. Until effective vaccines and/or therapeutics are available for use to prevent or treat LF, a better level of understanding of the basic biology of LASV, its natural genetic variations and immune evasion mechanisms as potential pathogenicity factors, and of the rodent reservoir-vector populations and their geographical distributions, is necessary for the development of accurate diagnostics and effective therapeutics and vaccines against this deadly human viral pathogen.

Purpose To investigate the anti-inflammatory and anti-fungal role of α-melanocyte stimulating hormone (α-MSH) in Aspergillus Fumigatus (A. fumigatus) keratitis. Method Corneas of C57BL/6 mice were infected with A. Fumigatus. α-MSH (5 ul, 1x10-4mmol/ml) was given by subconjunctival injection from day 1 to day 3 post infection (p.i.). After 3 days p.i., clinical score was recored and HE staining was tested. Fungal load in mice corneas was observed by plate counting. Pro-inflammatory mediators and pattern recognition receptors (PRRs) were detected. The numbers of neutrophils and macrophages were tested by immunofluorescence staining. The role of α-MSH in RAW264.7 cells after A. fumigatus stimulation were evaluated by PCR and Western blot, and MPKA protein levels including total-JNK (T-JNK), phosphorylated-JNK (P-JNK), total-ERK (T-ERK) and phosphorylated-ERK (P-ERK) were tested via Western blot with or without α-MSH treatment. Results Compared with PBS control group, α-MSH treatment alleviated disease response and decreased clinical score at 3 days p.i. HE staining showed less infiltration in corneal tissue after α-MSH treatment. Plate counting experiment showed that number of viable fungus in corneas of α-MSH treated group was less than control group. mRNA levels of IL-1β, TNF-α, IL-6, MIP-2, LOX-1, Dectin-1 and iNOS were decreased. Protein levels of IL-1β, TNF-α, IL-6 and Dectin-1 were decreased. α-MSH treatment also decreased the infiltrating neutrophils and macrophages. The levels of pro-inflammatory cytokines, Dectin-1 and LOX-1 stimulated by A. fumigatus, were also suppressed by pretreatment of α-MSH in RAW264.7 cells. The ratio of P-JNK/T-JNK and P-ERK/T-ERK were down regulated in α-MSH group compared with PBS control group. Conclusion α-MSH alleviates the severity and decreases fungal load of A. fumigatus keratitis in mice. Migration of neutrophils and macrophages are restrained. α-MSH downregulates the expression of dectin-1 and the ratio of P-JNK/T-JNK and P-ERK/T-ERK in A. fumigatus infection.

There is an ever-increasing range of antibiotic-resistant pathogens that have led to higher community-acquired infections, and substantial mortality rates in critically ill patients.We have critically appraised available evidence through a structured literature review, investigating effective empiric antibiotic administration and appropriateness on outcomes of critically ill patients with an increased risk of developing resistant pathogens. The use of new antibiotics should be determined based on relevant knowledge of their spectrum and properties to provide effective mode of action for critically ill patients.Restricting severely ill patients access to new broad-spectrum empirical drugs is not the answer. Rather there should be a focus on identifying host response to infection to differentiate between colonization or contamination and true infection, and the sensitivity to antibiotics used in the intensive care unit (ICU). Management relies on adequate antibiotic administration, the ability to monitor response, and facilitate the cessation of antibiotic treatment. The major determinant of patient success in a patient with a severe infection is the 'right' antibiotic or complementary course of treatment. As an overarching criterion, the following three appropriate "Ds" should be considered: Dosing, Duration, and De-escalation to empirically assess the right antibiotic optimal antimicrobial selection.

The present study utilized an in vitro dual-species biofilm model and an in vivo rat post-treatment endodontic disease (PTED) model to investigate whether co-infection of Candida albicans and Enterococcus faecalis would aggravate periapical lesions. The results showed that co-culturing yielded a thicker and denser biofilm more tolerant to detrimental stresses compared with the mono-species biofilm, such as a starvation-alkalinity environment, mechanical shear force and bactericidal chemicals. Consistently, co-inoculation of E. faecalis and C. albicans significantly increased the extent of in vivo periapical lesions compared with mono-species infection. Specifically, coexistence of both microorganisms increased osteoclastic bone resorption and suppressed osteoblastic bone formation. The synergistic effects also up-regulated inflammatory cytokines including TNF-α and IL-6. In summary, coexistence of C. albicans and E. faecalis increased periapical lesions by enhanced biofilm virulence.

Tobacco consumption is related to an increased risk to develop tuberculosis. Antimicrobial peptides are essential molecules in the response to Mycobacterium tuberculosis (Mtb) because of their direct antimicrobial activity. The aim of this study was to demonstrate that nicotine enters into Mtb infected epithelial cells and associates with the mycobacteria inducing genes related to antimicrobial peptides resistance. Epithelial cells were infected with virulent Mtb, afterwards cells were stimulated with nicotine. The internalization of nicotine was followed using electron and confocal microscopy. The lysX expression was evaluated isolating mycobacterial RNA and submitted to RT-PCR analysis. Our results indicated that nicotine promotes Mtb growth in a dose-dependent manner in infected cells. We also reported that nicotine induces lysX expression. In conclusion, nicotine associates to intracellular mycobacteria promoting intracellular survival.

The present study investigated the development of intestinal lactic acid bacteria (LAB) in piglets by high-throughput sequencing. Fresh feces from newborn piglets were collected at the ages of 1, 2, 3, 7, 14, 21, 24, 35 and 42 days. Sequencing of DNA amplicons of bacteria in feces amplified with LAB-specific primers showed that Lactobacillus was the predominant genus with an abundance higher than 70%, but tended to decrease after weaning (p = 0.059). The abundance of Streptococcus was the second predominant genus on day 1, then decreased significantly (p

Fasciolosis caused by the liver flukes Fasciola hepatica and Fasciola gigantica is one of the most important neglected parasitic diseases of humans and animals. The ability of the parasites to infect and multiply in their intermediate snail hosts, and their adaptation to a wide variety of mammalian definitive hosts contribute to their high transmissibility and distribution. Within the mammalian host, the trauma caused by the immature flukes burrowing through the liver parenchyma is associated with most of the pathogenesis. Similarly, the feeding activity and the physical presence of large flukes in the bile ducts can lead to anaemia, inflammation, obstruction and cholangitis. The high frequency of non-synonymous polymorphisms found in Fasciola spp. genes allows for adaptation and invasion of a broad range of hosts. This is also facilitated by parasite's excretory-secretory (ES) molecules that mediate physiological changes that allows their establishment within the host. ES contains cathepsin peptidases that aid parasite invasion by degrading collagen and fibronectin. In the bile ducts, cathepsin-L is critical to haemoglobin digestion during feeding activities. Other molecules (peroxiredoxin, cathepsin-L and Kunitz-type inhibitor) stimulate a strong immune response polarised towards a Treg/Th2 phenotype that favours fluke's survival. Helminth defence molecule, fatty acid binding proteins, Fasciola-specific glycans and miRNAs modulate host pro-inflammatory responses, while antioxidant scavenger enzymes work in an orchestrated way to deter host oxidant-mediated damage. Combining these strategies Fasciola spp. survive for decades within their mammalian host, where they reproduce and spread to become one of the most widespread zoonotic worm parasites in the world.

Made available in DSpace on 2022-05-01T10:35:01Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01 Fluconazole-sensitive (CaS) and -resistant (CaR) C. albicans were grown as single-species and dual-species biofilms with Lactobacillus casei (Lc) and Lactobacillus rhamnosus (Lr). Single-species Lc and Lr were also evaluated. Biofilm analysis included viable plate counts, the extracellular matrix components, biomass, and structural organization. Lc reduced the viability of CaS, water-soluble polysaccharides, and eDNA in CaS + Lc biofilm. Lc biofilm presented more eDNA than CaS. The total biomass of CaS + Lc biofilm was higher than the single-species biofilms. The viability of Lc and Lr was reduced by CaR dual-species biofilms. The total and insoluble biomass in CaS + Lr was higher than in single-species CaS biofilms. Lc hindered the growth of CaS, and their association hampered matrix components linked to the structural integrity of the biofilm. These findings allow understanding of how the implementation of probiotics influences the growth of C. albicans biofilms and thereby helps with the development of novel approaches to control these biofilms. Department of Dental Materials and Prosthodontics São Paulo State University (UNESP) School of Dentistry Department of Cariology Operative Dentistry & Dental Public Health Indiana University School of Dentistry Department of Surgery and Diagnosis São Paulo State University (Unesp) School of Dentistry Department of Dental Materials and Prosthodontics São Paulo State University (UNESP) School of Dentistry Department of Surgery and Diagnosis São Paulo State University (Unesp) School of Dentistry

Made available in DSpace on 2022-04-29T08:36:39Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01 This study evaluated the effect of sodium hexametaphosphate (HMP), administered alone or in combination with fluoride (F), on dual-species biofilms of Streptococcus mutans and Candida albicans. Biofilms were treated with HMP solutions at 0.25%, 0.5% and 1%, alone or combined with F (0.05%), and compared by evaluating their structure and quantifying the colony-forming units (CFUs), metabolic activity, production of biomass and extracellular matrix components. All HMP-containing solutions were capable of reducing metabolic activity, the biofilm biomass, and the extracellular matrix components. Furthermore, the treatment with 1% HMP/F significantly reduced the CFUs of S. mutans, although it showed no effect on the CFUs of C. albicans, in the dual-species biofilms. In general, the combination of HMP and F influenced all the parameters analyzed from dual-species biofilms, except the CFUs of C. albicans. Department of Preventive and Restorative Dentistry School of Dentistry Araçatuba São Paulo State University (UNESP) Graduate Program in Dentistry (GPD - Master’s Degree) University of Western São Paulo (UNOESTE) Department of Preventive and Restorative Dentistry School of Dentistry Araçatuba São Paulo State University (UNESP)

Staphylococcus pseudintermedius is increasingly recognized as a human pathogen. We report the first case of an urinary tract infection in a male patient with this organism.

Vertebrate-parasitic nematodes cause debilitating, chronic infections in millions of people worldwide. The burden of these so-called ‘neglected tropical diseases’ is often carried by poorer socioeconomic communities in part because research on parasitic nematodes and their vertebrate hosts is challenging and costly. However, complex biological and pathological processes can be modeled in simpler organisms. Here, we consider how insight into the interactions between entomopathogenic nematodes (EPN), their insect hosts and bacterial symbionts may reveal novel treatment targets for parasitic nematode infections. We argue that a combination of approaches that target nematodes, as well as the interaction of pathogens with insect vectors and bacterial symbionts, offer potentially effective, but underexplored opportunities.

CRISPR/Cas9 genome editing systems have been established in a broad range of eukaryotic species. Herein, we report the first method for genetic engineering in pyogo (shiitake) mushrooms (Lentinula edodes) using CRISPR/Cas9. For in vivo expression of guide RNAs (gRNAs) targeting the mating-type gene HD1 (LeA1), we identified an endogenous LeU6 promoter in the L. edodes genome. We constructed a plasmid containing the LeU6 and glyceraldehyde-3-phosphate dehydrogenase (LeGPD) promoters to express the Cas9 protein. Among the eight gRNAs we tested, three successfully disrupted the LeA1 locus. Although the CRISPR-Cas9–induced alleles did not affect mating with compatible monokaryotic strains, disruption of the transcription levels of the downstream genes of LeHD1 and LeHD2 was detected. Based on this result, we present the first report of a simple and powerful genetic manipulation tool using the CRISPR/Cas9 toolbox for the scientifically and industrially important edible mushroom, L. edodes.

Introduction As a biofilm-associated disease, dental caries benefits from nanoparticle (NP)-based therapies. Streptococcus mutans (S. mutans) is a primary aetiologic agent for dental caries development. We successfully applied a synergistic therapy of Ag/ZnO nanocomposites combined with light-emitting diode (LED) radiation to inhibit S. mutans biofilms. However, the antibiofilm mechanism has not been fully elucidated, and little is known about the biofilm formation ability of bacteria that survive NP-based therapies. Methods This study explored the antibiofilm formation mechanism of this synergistic therapy by an integrated approach based upon proteomics. Results Synergistic therapy killed 99.8% of bacteria, while the biofilm formation ability of 0.2% surviving bacteria was inhibited. The proteomic responses of S. mutans to synergistic therapy were comprehensively characterized to unveil the mechanism of bacterial death and biofilm formation inhibition of the surviving bacteria. In total, 55 differentially expressed proteins (12 upregulated and 43 downregulated) were recorded. The bioinformatic analysis demonstrated that cellular integrity damage and regulated expression of structure-associated proteins were the main reasons for bacterial death. In addition, the proteomic study indicated the potential inhibition of metabolism in surviving bacteria and provided a biofilm-related network consisting of 17 differentially expressed proteins, explaining the multiantibiofilm formation actions. Finally, we reported and verified the inhibitory effects of synergistic therapy on sucrose metabolism and D-alanine metabolism, which disturbed the biofilm formation of surviving bacteria. Conclusion Our findings demonstrated that synergistic therapy killed most bacteria and inhibited the surviving bacteria from forming biofilms. Furthermore, the antibiofilm formation mechanism was revealed by proteomics analysis of S. mutans after synergistic therapy and subsequent metabolic studies. Our success may provide a showcase to explore the antibiofilm formation mechanism of NP-based therapies using proteomic studies., Graphical Abstract

Oki Suwarsa, Maryam Nissa Hazari, Hartati Purbo Dharmadji, Reiva Farah Dwiyana, Raden Mohamad Rendy Ariezal Effendi, Risa Miliawati Nurul Hidayah, Erda Avriyanti, Hendra Gunawan, Endang Sutedja Department of Dermatology and Venereology, Faculty of Medicine, Universitas Padjadjaran - Dr. Hasan Sadikin General Hospital, Bandung, West Java, IndonesiaCorrespondence: Hendra GunawanDepartment of Dermatology and Venereology, Faculty of Medicine, Universitas Padjadjaran - Hasan Sadikin General Hospital, Pasteur 38, Bandung, West Java, 40161, IndonesiaTel +62 222032426 ext. 3449Fax +62 222032426Email h.gunawan2016@unpad.ac.idBackground: Atopic dermatitis (AD) interferes with quality of life and is influenced by important factors like skin microbiome. The results of the skin microbiome composition and diversity in AD varied in some studies.Purpose: This study aims to determine the composition and diversity of the skin microbiome in Indonesian AD patients.Patients and Methods: Genomic deoxyribonucleic acid (DNA) preparations were obtained from skin swabs of the cubital fossa of 16 subjects, nine of which were having mild AD, three moderate AD, and four healthy individuals. DNA extraction and sequencing of the 16S ribosomal ribonucleic acid (rRNA) gene using next-generation sequencing and bioinformatics analysis were further performed.Results: Firmicutes (p), Bacilli (c), Bacillales (o), Staphylococcaceae (f), and Staphylococcus (g) were dominant in moderate AD. On the contrary, Proteobacteria (p), Gammaproteobacteria (c), Pseudomonadales (o), Moraxellaceae (f), and Acinetobacter (g) were dominant in mild AD. Staphylococcus aureus was found in the highest number in individuals with moderate AD. Interestingly, Ensifer adhaerens was found in mild AD. Microbial diversity was decreased in moderate AD.Conclusion: Metagenomic analysis in this study identified microbes in moderate and mild AD and showed a low diversity of skin microbiomes in moderate AD. Interestingly, this is the first time that the bacteria Ensifer adhaerens was detected on the human skin.Keywords: atopic dermatitis, microbiome, skin microbiome

Background Klebsiella pneumoniae is armed with a wide range of antibiotic resistance mechanisms that mostly challenge effective treatment. The aims of the current study were to identify the clinical strains of K. pneumoniaealso to determine their phenotypes and molecular characterization related to antimicrobial resistance and virulence genes. Research design and methods In this investigation, clinical specimens from different hospitals located in Tehran, Iran, were collected during a nine-month period (December 2018 to August 2019). The K. pneumoniae strains were isolated and identified through standard microbial and biochemical assays. Additionally, disk diffusion, combined disk, Modified Hodge Test (MHT) and PCR were performed for antibiotic resistance and virulence gene analysis, respectively. Results Eighty-four isolates of K. pneumoniae were subjected to the study. According to the combined disk and modified Hodge test results, 27 (52%) and 15 pathotypes (62.5%) out of resistant strains of isolated K. pneumoniae were detected as ESBL and KPC producers. The virulence genes of mrkD (94%) and magA (11%) were the highest and lowest among isolates, respectively. Conclusions The high prevalence of antibiotic resistance and virulence genes in conjunction with a significant relationship between the strains revealed a high pathogenic capacity of the isolated pathotypes of K. pneumoniae.

Made available in DSpace on 2022-05-01T10:18:54Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01 Polymicrobial biofilms comprising Candida albicans and Staphylococcus aureus can increase the frequency and severity of oral diseases. This study assessed oral keratinocyte cell death, apoptosis and/or necrosis, promoted by soluble factors from single and dual biofilms of S. aureus and C. albicans. The soluble factors were obtained from the 16-h biofilm growth media. Cell viability was assessed by MTT and cell membrane damage by LDH. SEM was used for morphology changes. Assessment of apoptosis and necrosis was performed using annexin V and propidium iodide and caspases -2, -3, -6, -8 and -9. Statistical analysis was conducted with ANOVA and Tukey tests (α = 5%). Dual biofilms promoted the greatest harmful effect on oral cells, with a viability rate of 31.76%, damage to cell membranes and LDH released. Dual biofilms also induced higher percentages of necrotic cells (24.95%). Apoptosis was associated with caspases -2, -3, -6 and -8 activation. Department of Dental Materials and Prosthodontics School of Dentistry São Paulo State University (UNESP) Department of Dental Materials and Prosthodontics School of Dentistry São Paulo State University (UNESP)

Streptomyces is the largest and most significant genus of Actinobacteria, comprising 961 species. These Gram-positive bacteria produce many versatile and important bioactive compounds; of these, antibiotics, specifically the enhancement or activation of their production, have received extensive research attention. Recently, various biotic and abiotic elicitors have been reported to modify the antibiotic metabolism of Streptomyces, which promotes the production of new antibiotics and bioactive metabolites for improvement in the yields of endogenous products. However, some elicitors that obviously contribute to secondary metabolite production have not yet received sufficient attention. In this study, we have reviewed the functions and mechanisms of chemicals, novel microbial metabolic elicitors, microbial interactions, enzymes, enzyme inhibitors, environmental factors, and novel combination methods regarding antibiotic production in Streptomyces. This review has aimed to identify potentially valuable elicitors for stimulating the production of latent antibiotics or enhancing the synthesis of subsistent antibiotics in Streptomyces. Future applications and challenges in the discovery of new antibiotics and enhancement of existing antibiotic production using elicitors are discussed.

A broad-spectrum antimicrobial peptide named Paracin 1.7 was produced by Lactobacillus paracasei HD1.7, which was isolated from Chinese sauerkraut juice. In this study, the influence of cocultivation on the communication mechanism of L. paracasei HD1.7 and Bacillus subtilis was investigated. The two bacterial strains were grown in monoculture and indirect coculture, and the growth of both bacteria and bacteriocin production as well as the transcriptional level of luxS in L. paracasei HD1.7 and spo0A in B. subtilis were monitored. Bacteriocin production and cell numbers were increased significantly when L. paracasei HD1.7 cells were indirectly cocultured with B. subtilis, and bacteriocin-producing L. paracasei HD1.7 can prevent the growth and sporulation of B. subtilis. After indirect coculture with B. subtilis, the expression of luxS in L. paracasei HD1.7 increased in the exponential growth phase and decreased in the stationary phase compared to monoculture. The expression of spo0A in B. subtilis dropped in the indirect coculture compared to the monoculture. It indicate that the upregulation of luxS is due to a response to a secreted compound produced by B. subtilis. The results show L. paracasei HD1.7 has an amensalism on B. subtilis, while B. subtilis has a commensalism on L. paracasei HD1.7.

Wastes liberation from mining operations has occurred for quite a few centuries, and quarrying has advanced considerably in the twentieth century. Minerals excavating and their further processing g...

We designed a bacteria-targeting and membrane disrupting nanocomposite for successful antibiotic treatment of Helicobacter pylori (H. pylori) infections in the present study. The antibacterial nanocomposite was prepared from thiolated-ureido-chitosan (Cys-U-CS) and anionic poly (malic acid) (PMLA) via electrostatic interaction decorated with dual functional ammonium citrate carbon quantum dots (CDs). Cys-U-CS serves as a targeting building block for attaching antibacterial nanocomposite onto bacterial cell surface through Urel-mediated protein channel. Simultaneously, membrane disrupting CDs generate ROS and lyse the bacterial outer membrane, allowing antibiotics to enter the intracellular cytoplasm. As a result, Cys-U-CS/PMLA@CDs nanocomposite (UCPM-NPs) loaded with the antibiotic amoxicillin (AMX) not only effectively target and kill bacteria in vitro via Urel-mediated adhesion but also efficiently retain in the stomach where H. pylori reside, serving as an effective drug carrier for abrupt on-site release of AMX into the bacterial cytoplasm. Furthermore, since thiolated-chitosan has a mucoadhesive property, UCPM-NPs may adhere to the stomach mucus layer and pass through it swiftly. According to our results, bacterial targeting is crucial for guaranteeing successful antibiotic treatment. The bacteria targeting UCPM-NPs with membrane disruptive ability may establish a promising drug delivery system for the effective targeted delivery of antibiotics to treat H. pylori infections.

Background Treatment and control of schistosomiasis rely on a single drug, praziquantel. New orally active antischistosomals featuring novel molecular scaffolds are urgently needed to prevent the emergence of resistance. Methods We screened 400 drug-like compounds contained in the open-access Pandemic Response Box (PRB) against newly transformed schistosomula (NTS) at a concentration of 10 µM scoring death, changes in motility, and morphological alterations. Compounds displaying an activity ≥66% at 72 h underwent testing against adult Schistosoma mansoni in vitro. Fast-acting (≥66% at 24 h), nontoxic drugs focusing on late-stage and approved drugs were investigated in the patent S. mansoni mouse model. Results We identified 26 hits active against NTS, of which 17 elicited ≥66% activity against adult S. mansoni following 24 h of drug exposure. The highest activity against adult S. mansoni was observed with MMV1581558 (EC50 value of 0.18 ± 0.01 µM) and nitazoxanide (0.47 ± 0.07 µM). Of the five compounds tested in vivo, MMV1581558 and the approved drug ozanimod reduced average worm burden versus controls by 42 % and 36 %, respectively, after a single oral dose of 200 mg/kg bodyweight in mice harboring a chronic S. mansoni infection. Conclusion MMV1581558 discovered from screening the PRB represents a novel antischistosomal scaffold with high in vitro antischistosomal activity amenable to chemical modification for drug development.

Helicobacter pylori (H. pylori) has occupied a significant place among infectious pathogens and it has been documented as a leading challenge due to its higher resistance to the commonly used drugs...

Anthropogenic activities are often related to the occurrence of simultaneous contaminations with heavy metals and toxic organic compounds. In addition, the increasing demand for food, clothing, and technology has increased the worldwide contamination level. Although it is not fully demonstrated, the high level of contamination in association with the indiscriminate use of antibiotics, led to the appearance of multi-resistant pathogenic microorganisms. Grey and red biotechnologies try to counteract the negative effects of pollution and antimicrobial resistance respectively. Streptomyces is well known in the field of biotechnology. In this review, we discussed the potential of these bacteria to deal with organic and inorganic pollutants and produce nanostructures with antimicrobial activity. To our knowledge, this is the first work in which a biotechnological bacterial genus such as Streptomyces is revised in two different fields of global concern, contamination, and multi-drugs resistant microorganisms.

We found that the expression of genes involved in kojic acid (KA) biosynthesis, kojA, kojR, and kojT, was highly elevated in the Aspergillus oryzae autophagy-deficient mutants. In agreement, KA production was much increased in these mutants. Nuclear translocation of KojR, a transcription factor, was observed in the autophagy mutants before they were starved, explaining why KA production was boosted.

Representatives of the genus Bacillus are multifunctional microorganisms with a broad range of applications in both traditional fermentation and modern biotechnological processes. Bacillus spp. has several beneficial properties. They serve as starter cultures for various traditional fermented foods and are important biotechnological producers of enzymes, antibiotics, and bioactive peptides. They are also used as probiotics for humans, in veterinary medicine, and as feed additives for animals of agricultural importance. The beneficial effects of bacilli are well-reported and broadly acknowledged. However, with a better understanding of their positive role, many questions have been raised regarding their safety and the relevance of spore formation in the practical application of this group of microorganisms. What is the role of Bacillus spp. in the human microbial consortium? When and why did they start colonizing the gastrointestinal tract (GIT) of humans and other animals? Can spore-forming probiotics be considered as truly beneficial organisms, or should they still be approached with caution and regarded as "benefits with concerns"? In this review, we not only hope to answer the above questions but to expand the scope of the conversation surrounding bacilli probiotics.

A hospital-based cross-sectional study was conducted during 2018-2019 to decipher the prevalence of yeast mastitis. The results indicated a 19.68% prevalence of clinical mastitis in bovines. Among them, 5.51% of samples revealed yeasts constituting 1.09% overall prevalence. Candida albicans was recorded as a significant fungal agent involved in clinical bovine mastitis. We record the association of Kodamaea ohmeri in clinical bovine mastitis. On proteomic and molecular confirmation, K. ohmeri isolates were re-identified from phenotypically identified Candida isolates associated with bovine mastitis. After conventional identification, the yeast isolates were re-identified by MALDI-TOF MS-based proteomic approaches. The D1/D2 domains of 26S-rRNA gene and 5.8S-internal transcribed spacer (ITS) rDNA regions based molecular phylogenetic analysis identified the isolates as K. ohmeri. The isolates were resistant to fluconazole. This study reports the first systemic study of K. ohmeri isolates recovered from bovine clinical mastitis, utilizing conventional, automated, proteomic, and genomic approaches followed by antifungal susceptibility. The findings suggest K. ohmeri as a potent opportunistic emerging pathogen of veterinary and public health concern, need for accurate identification of fungal agents from mycotic mastitis, and use of validated antifungal susceptibility assay because of developing resistance to antimycotic agents. Our findings suggest judicious use of fluconazole and alternative antifungal agents may be considered in case of an outbreak.

Listeria monocytogenes is a saprophytic gram-positive bacterium, and an opportunistic foodborne pathogen that can produce listeriosis in humans and animals. It has evolved an exceptional ability to adapt to stress conditions encountered in different environments, resulting in a ubiquitous distribution. Because some food preservation methods and disinfection protocols in food-processing environments cannot efficiently prevent contaminations, L. monocytogenes constitutes a threat to human health and a challenge to food safety. In the host, Listeria colonizes the gastrointestinal tract, crosses the intestinal barrier, and disseminates through the blood to target organs. In immunocompromised individuals, the elderly, and pregnant women, the pathogen can cross the blood-brain and placental barriers, leading to neurolisteriosis and materno-fetal listeriosis. Molecular and cell biology studies of infection have proven L. monocytogenes to be a versatile pathogen that deploys unique strategies to invade different cell types, survive and move inside the eukaryotic host cell, and spread from cell to cell. Here, we present the multifaceted Listeria life cycle from a comprehensive perspective. We discuss genetic features of pathogenic Listeria species, analyze factors involved in food contamination, and review bacterial strategies to tolerate stresses encountered both during food processing and along the host’s gastrointestinal tract. Then we dissect host–pathogen interactions underlying listerial pathogenesis in mammals from a cell biology and systemic point of view. Finally, we summarize the epidemiology, pathophysiology, and clinical features of listeriosis in humans and animals. This work aims to gather information from different fields crucial for a comprehensive understanding of the pathogenesis of L. monocytogenes., Graphical abstract

Aspergillus oryzae is an ideal host for expressing heterologous and homologous genes. Due to the risk of antibiotics to food safety, it is banned for use in resistance screening with food-grade exp...

Yajun Zhang,1,* Biao Meng,2,3,* Xiao Wei,2,* Yan Li,2 Xiaohui Wang,1 Yan Zheng,1 Changjun Wang,2,3 Lihong Cui,1 Xiangna Zhao2,3 1Department of Gastroenterology, The Sixth Medical Center of PLA General Hospital, Beijing, People’s Republic of China; 2Centre for Disease Control and Prevention of China PLA, Beijing, People’s Republic of China; 3Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lihong Cui; Xiangna Zhao Tel +86-10-66948393Fax +86-10-66948304Email luckycui861@sina.com; xnazhao@163.comBackground: Pseudomonas aeruginosa is an important nosocomial infectious bacterium, more and more multidrug resistant P. aeruginosa have been isolated and posed severe challenges to clinical antibiotic treatment, bringing additional morbidity, mortality, and economic burden. Bacteriophages can lyse bacteria specificity and are feasible alternatives to antibiotics.Methods: A Pseudomonas aeruginosa-infecting phage vB_PaeP_PA01EW was isolated. Phage plaque assays, transmission electron microscopy, host-range determination, infection assay analyses, whole-genome sequencing and annotation were performed for the phage. Mice pneumonia model using liquid aerosol-exposure Pseudomonas aeruginosa was established, and phage therapy was evaluated.Results: vB_PaeP_PA01EW belongs to the family Podoviridae according to transmission electron microscopy and was identified as a Luz24likevirus according to the genome analysis. For the phage therapy, compared with the bacteria-infected group, the phage-rescue group has some characteristics. First, adventitial edema and diffuse infiltration of inflammatory cells in tissues were alleviated, Second, bronchial epithelial cell proliferation was reduced. Third, the bacterial burden was significantly decreased.Conclusion: This study provided data support and theoretical basis for the clinical application of bacteriophages. It has important guiding significance and reference value for the application of bacteriophage therapy of other pathogenic bacteria.Keywords: P. aeruginosa, bacteriophage, vB_PaeP_PA01EW, aerosol-exposure

Huaiyu Jia,1 Ying Zhang,2 Jianzhong Ye,1 Wenya Xu,1 Ye Xu,1 Weiliang Zeng,2 Wenli Liao,1 Tao Chen,1 Jianming Cao,2 Qing Wu,1 Tieli Zhou1 1Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, People’s Republic of China; 2Department of Medical Laboratory Science, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang Province, People’s Republic of ChinaCorrespondence: Tieli Zhou; Qing WuDepartment of Clinical Laboratory, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of ChinaTel/Fax +86-0577-8668-9885Email wyztli@163.com; wuqing830@163.comBackground: OXA-232-producing carbapenem-resistant Klebsiella pneumoniae (CRKP) has the potential to become the “third epidemic” of carbapenem-resistant Klebsiella strain after KPC-2 and NDM in China. We investigated the first outbreak of CRKP in the First Affiliated Hospital of Wenzhou Medical University.Methods: We collected 610 clinical isolates of CRKP from the First Affiliated Hospital of Wenzhou Medical University between January 2019 and September 2020 and screened them by Polymerase Chain Reaction (PCR). The multilocus sequence typing and pulsed-field gel electrophoresis were used to determine the genetic relatedness of the strains. The antimicrobial susceptibility test was performed to determine the drug resistance of the clinical isolates. The molecular mechanism underlying carbapenem resistance was elucidated by performing PCR and conjugation experiments. The virulence potential of the strains was determined by the string test, detection of virulence-associated genes and capsular serotypes, and Galleria mellonella larval infection model.Results: Between September 2019 and May 2020, 26 OXA-232-producing CRKP were obtained from 12 patients in our hospital. Ten patients were hospitalized in the intensive care units (ICU) and the overall mortality of the inpatients involved in the outbreak was 50% (6/12). Epidemiological investigations reported that all the OXA-232-producing CRKP strains belonged to the sequence type ST15 and can be clonally transmitted among the inpatients in the ICU. All the strains had low virulence and were resistant to commonly used clinical antibiotics except for ceftazidime/avibactam, colistin, and tigecycline. The OXA-232-producing CRKP was sensitive to triclosan and chlorhexidine, and its eradication from our hospital can be achieved by the use of disinfectants in the ICU.Conclusion: In our study, OXA-232-producing CRKP isolates appeared to be clonally transmitted and the sequence type ST15 was responsible for the outbreak. Therefore, effective measurements for the infection control of CRKP are urgently needed to prevent its epidemic in the nearby region in the future.Keywords: Klebsiella pneumoniae, carbapenem-resistance, virulence, OXA-232, outbreak

Lianjiang Huang,1 Li Fu,2 Xiaoyan Hu,3 Xiaoliang Liang,1 Guozhong Gong,4 Chunhong Xie,1 Feiyang Zhang,3 Ying Wang,3 Yingshun Zhou3 1Department of Clinical Laboratory, The Second Affiliated Hospital of Xiamen Medical College, Xiamen, 361021, People’s Republic of China; 2The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 3Department of Pathogen Biology, School of Basic Medicine, Public Center of Experimental Technology of Pathogen Biology Technology Platform, Southwest Medical University, Luzhou, 646000, People’s Republic of China; 4Department of Clinical Laboratory, Suining First People’s Hospital, Suining, 629000, People’s Republic of ChinaCorrespondence: Yingshun Zhou; Ying WangDepartment of Pathogen Biology, School of Basic Medicine, Public Center of Experimental Technology of Pathogen Biology Technology Platform, Southwest Medical University, No. 1, Xianglin Road, Luzhou, 646000, People’s Republic of ChinaTel +86-830-3160073Email yingshunzhou@swmu.edu.cn; wyingnbgg@163.comObjective: The aim of this study was to use whole-genome sequencing to characterize Klebsiella pneumoniae SKp2F and Klebsiella variicola SKv2E, both carrying blaKPC, co-isolated from the same sputum specimen.Methods: Antimicrobial susceptibility testing was performed using microbroth dilution. Biofilm formation was determined by crystal violet staining and virulence was measured by a serum killing assay. Whole-genome sequencing of SKp2F and SKv2E was performed using an Illumina sequencer and the genetic characteristics were analyzed by computer.Results: SKp2F and SKv2E were sensitive only to tigecycline and polymyxin among the tested antibiotics. The biofilm-forming ability of SKv2E is stronger than that of SKp2F. The grades of serum resistance of SKp2F and SKv2E are 4 and 3. MLST analysis of the 6,115,610 bp and 5,403,687 bp of SKv2E and SKp2F showed associations with ST1615 and ST631, respectively. SKv2E carried 13 resistance genes (blaKPC-2, blaTEM-1A, blaLEN17, aadA16, arr-3, qnrB4, oqxA/B, dfrA27, sul1, tetD, fosA, qacEΔ 1) and SKp2F carried 23 (blaKPC-2, blaCTX-M-3, blaTEM-1B, blaCTX-M-65, blaSHV-27, aac(6ʹ)-IIa, rmtB, arr-3, aph(3ʹ)-Ia, aadA16, qnrS1, aac(6ʹ)-Ib-cr, qnrB91, oqxA/B, mph(A), tet(A), fosA, dfrA27, and two copies of qacEΔ 1-sul1). Most of them were carried by various mobile genetic elements, such as IncFIB(K)/IncFII(K)/IncFII(Yp), IncFII(K) plasmid, Tn6338, and In469. Both SKv2E and SKp2F carried a large number of virulence factors, including type 1 and 3 fimbriae, capsule, aerobactin (iutA), ent siderophore (entABCDEFS, fepABCDGfes), and salmochelin (iroE/iroEN). SKv2E also carried type IV pili (pilW), fimbrial adherence (steB, stfD), and capsule biosynthesis gene (glf).Conclusion: blaKPC-2-carrying K. variicola and K. pneumoniae, which carried multiple resistance genes, virulence factors, and highly similar mobile genetic elements, were identified from the same specimen, indicating that clinical samples may carry multiple bacteria. We should avoid misidentification, and bear in mind that resistance genes carrying mobile genetic elements can be transmitted or integrated between bacteria in the same host.Keywords: Klebsiella variicola, Klebsiella pneumoniae, carbapenem-resistant Enterobacteriaceae, CRE, blaKPC

Yahong Zheng,1 Yuting Ding,1 Mengran Xu,1 Haoran Chen,1 Hui zhang,1 Yanyan Liu,1– 3 Weihua Shen,4 Jiabin Li1– 3,5 1Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Anhui Center for Surveillance of Bacterial Resistance, Hefei, Anhui, People’s Republic of China; 3Institute of Bacterial Resistance, Anhui Medical University, Hefei, Anhui, People’s Republic of China; 4Department of Special Clinic, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 5Department of Infectious Diseases, The Chaohu Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of ChinaCorrespondence: Jiabin LiDepartment of Infectious Diseases, The First Affiliated Hospital and the Chaohu Hospital of Anhui Medical University, Jixi road 218, Hefei, Anhui, 230022, People’s Republic of ChinaEmail lijiabin@ahmu.edu.cnWeihua ShenDepartment of Special Clinic, The First Affiliated Hospital of Anhui Medical University, Jixi road 218, Hefei, Anhui, 230022, People’s Republic of ChinaEmail Shenweihua2021810@163.comPurpose: Klebsiella pneumoniae-induced liver abscess (KLA) is a type of pyogenic liver abscess (PLA), which is a distinct invasive syndrome that has been increasingly reported worldwide over the past two decades. The intestinal microbiota is increasingly recognized as an important modulator that can promote and maintain host immune homeostasis. However, its precise role in liver abscess is unknown. We aimed to investigate the function of the gut microbiota in the host defense against K. pneumoniae infection.Methods: We constructed C57BL/6J mice with KLA and analyzed the diversity and richness of the intestinal microflora by 16S rRNA sequencing. Next, to create a microbiota-depleted (MD) mouse model, we administered multiple broad-spectrum antibiotics and validated the model using 16S rRNA sequencing. At 48 h after K. pneumoniae infection, we assessed the general health condition, liver injury, bacterial loads, and inflammatory factor levels in MD+KLA mice. Additionally, fecal microbiota transplantation (FMT) was conducted in another group of MD+KLA mice prior to K. pneumoniae infection, and we assessed whether the transplantation changed the outcomes.Results: The diversity of the intestinal flora was significantly changed in KLA mice compared to control mice, with a decrease in beneficial bacteria and an increase in harmful bacteria. The MD+KLA mice exhibited impaired antimicrobial capacity, reduced survival, increased inflammation and liver damage at 48 h after K. pneumoniae infection compared to the KLA mice. However, FMT normalized the inflammatory cytokine levels, reduced liver damage, and increased survival.Conclusion: This study identified the gut microbiota as a protective factor against K. pneumoniae infection. The role of FMT in KLA should be investigated in future clinical studies.Keywords: Klebsiella pneumoniae, liver abscess, gut microbiome, fecal microbiota transplantation, inflammation

Histological investigations elucidate infection structure development and the subsequent colonization process of rust pathogens in their cereal hosts. No comprehensive information exists for the in...

Bioremediation using microorganisms have become innovative efficient tools for detoxifying a wide variety of urban and industrial wastewaters. In this study, we investigated for the first time the ...

Rubichaetoglobin A (1), a new cytochalasan alkaloid, together with nine closely related known ones (2-10), were isolated from the ethyl acetate extracts of the endophytic fungus Chaetomium tectifimeti S104 harbored in the root of Rubia podantha Diels. Their structures were elucidated based on comprehensive spectroscopic analysis. All isolated compounds were tested for cytotoxic, antibacterial, and nitric oxide inhibitory activities. The results showed that 2, 4, and 5 possessed moderate cytotoxicity against MDA-MB-231 cells with the IC50 values of 19.14, 11.43, and 10.27 μM, respectively.

Evidence suggests that Coxiella burnetii, which is shed in the milk, urine, feces, and birth products of infected domestic ruminants, can lead to Q fever disease following consumption of unpasteurized dairy products; however, C. burnetii is not believed to be a major gastrointestinal pathogen. Most infections are associated with inhalation of aerosols generated from the excreta of domestic ruminants. We recently demonstrated that C. burnetii delivered by oral gavage (OG) resulted in dissemination and an immune response; however, it is unclear how infection via the oral route compares to other well-established routes. Therefore, we delivered three strains of C. burnetii (representing three pertinent sequence types in the United States, such as ST16, ST20, and ST8) to immunocompetent mice in four doses via aerosol challenge (AC), intraperitoneal injection (IP), or OG. Low dose (10^5) of ST16 by OG was insufficient to cause infection, yet doses 1,000- or 100-fold lower by IP or AC, respectively, induced a robust immune response and dissemination. Despite being able to induce an immune response in a dose-dependent manner, administration of C. burnetii via OG is the least efficient route tested. Not only were the immune responses and bacterial loads diminished in mice exposed by OG relative to AC or IP, the efficiency of transmission was also inferior. High doses (10^8) were not sufficient to ensure transmission to 100% of the ST20 or ST8 cohorts. These results may provide some basis for why ingestion of C. burnetii as a mode of Q fever transmission is not often reported.

Published online: 27 Sep 2021., Helicobacter pylori is the major component of the gastric microbiome of infected individuals and one of the aetiological factors of chronic gastritis, peptic ulcer disease and gastric cancer. The increasing resistance to antibiotics worldwide has made the treatment of H. pylori infection a challenge. As a way to overhaul the efficacy of currently used H. pylori antibiotic-based eradication therapies, alternative treatment strategies are being devised. These include probiotics and prebiotics as adjuvants in H. pylori treatment, antimicrobial peptides as alternatives to antibiotics, photodynamic therapy ingestible devices, microparticles and nanoparticles applied as drug delivery systems, vaccines, natural products, and phage therapy. This review provides an updated synopsis of these emerging H. pylori control strategies and discusses the advantages, hurdles, and challenges associated with their development and implementation. An effective human vaccine would be a major achievement although, until now, projects regarding vaccine development have failed or were discontinued. Numerous natural products have demonstrated anti-H. pylori activity, mostly in vitro, but further clinical studies are needed to fully disclose their role in H. pylori eradication. Finally, phage therapy has the potential to emerge as a valid alternative, but major challenges remain, namely the isolation of more H. pylori strictly virulent bacterio(phages)., This work was supported by the Portuguese Foundation for Science and Technology – Fundação para a Ciência e Tecnologia (FCT) under the scope of the strategic funding of UIDB/04469/2020 unit, and Project PTDC/SAU-PUB/29182/2017 [POCI-01-0145-FEDER-029182]. RF is recipient of a FCT PhD grant with the reference SFRH/BD/146496/2019., info:eu-repo/semantics/publishedVersion

Helicobacter pylori infection is the principal cause of serious diseases (e.g. gastric cancer and peptic ulcers). Antibiotic therapy is an inadequate strategy in H. pylori eradication because of which vaccination is an inevitable approach. Despite the presence of countless vaccine candidates, current vaccines in clinical trials have performed with poor efficacy which makes vaccination extremely challenging. Remarkable advancements in immunology and pathogenic biology have provided an appropriate opportunity to develop various epitope-based vaccines. The fusion of proper antigens involved in different aspects of H. pylori colonization and pathogenesis as well as peptide linkers and built-in adjuvants results in producing epitope-based vaccines with excellent therapeutic efficacy and negligible adverse effects. Difficulties of the in vitro culture of H. pylori, high genetic variation, and unfavourable immune responses against feeble epitopes in the complete antigen are major drawbacks of current vaccine strategies that epitope-based vaccines may overcome. Besides decreasing the biohazard risk, designing precise formulations, saving time and cost, and induction of maximum immunity with minimum adverse effects are the advantages of epitope-based vaccines. The present article is a comprehensive review of strategies for designing and developing epitope-based vaccines to provide insights into the innovative vaccination against H. pylori.

Fumonisins are one of the most important mycotoxin classes due to their widespread occurrence and potential health threat to humans and animals. Currently, most of the research focuses on the control of fumonisin contamination in the food supply chain. In recent years, significant progress in biochemistry, enzymology, and genetic regulation of fumonisin biosynthesis has been achieved using molecular technology. Furthermore, new insights into the roles of fumonisins in the interaction between fungi and plant hosts have been reported. This review provides an overview of the current understanding of the biosynthesis and regulation of fumonisins. The ecological significance of fumonisins to Fusarium species that produce the toxins is discussed, and the complex regulatory networks of fumonisin synthesis is proposed.

Two new α-pyrones, micropyrones A (1) and B (2), along with four known γ-pyrones, nocapyrone D (3), nocapyrone A (4), marinactinone A (5), and nocapyrone H (6), were isolated from the culture extract of actinomycete Microbacterium sp. GJ312, which was isolated from Glycyrrhiza uralensis. The structures of these compounds were identified by analysis of spectral data. They are the first α- and γ-pyrones reported from the genus Microbacterium. The antibacterial activity of all compounds against Staphylococcus aureus and methicillin resistant S. aureus was evaluated. However, none of them showed significant activity. This study represents the first phytochemical example of a Glycyrrhiza-derived actinomycete.

This study aimed to evaluate the in vitro effect of aloe emodin, barbaloin and chrysophanol on growing and mature biofilms of Cryptococcus neoformans sensu stricto. The compounds were added at the moment of inducing biofilm growth or after growth for 72 h to evaluate their effects on growing and mature biofilms, respectively. Then, biofilm biomass was evaluated by crystal violet staining and metabolic activity by the XTT reduction assay. Morphological alterations were also evaluated by laser scanning confocal microscopy. Aloe emodin and barbaloin affected growing biofilms and disrupted mature biofilms, reducing metabolic activity by > 60% and biomass by > 70%. Chrysophanol only inhibited mature biofilms, but to a lesser extent. In conclusion, anthraquinones, especially aloe emodin and barbaloin, show a relevant effect against growing and mature biofilms of C. neoformans sensu stricto.