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The National Park of Hainan Tropical Rainforest (NPHTR) plays the crucial role of an ecological barrier for Hainan Island. It also serves as a valuable repository of tropical biological heritage for the world. The scientific establishment of an ecological security pattern (ESP) for the NPHTR is therefore essential for ensuring the robustness and stability of this regional ecosystem, safeguarding tropical biodiversity, and promoting sustainable development. This study integrates ecosystem service functions (ESFs) and ecological sensitivity to identify ecological sources (ESs) so that regional integrity is promoted and ecological security is ensured. Ecological corridors (ECs) are established on the basis of a minimum cumulative resistance (MCR) model and circuit theory. We integrate ESs, nodes, and corridors to construct the ESP of the NPHTR. The areas of extreme importance and sensitivity in the NPHTR account for 25.17% and 25.47% of its overall area, respectively, and are predominantly situated in the higher elevations of its eastern and central regions. Further, the ESs are mainly distributed in its western region, specifically Ba Wangling (BWL), Jian Fengling (JFL), and Ying Geling (YGL), covering an area of 1624.67 km2 (38.06% of the total area) of the NPHTR. After correction, 47 ECs with a distance of 870.9 km have been established, with BWL and YGL serving as the core areas. The ecological pinch- and barrier points in the NPHTR cover areas of 11.49 km2 and 16.35 km2, respectively, primarily consisting of man-made landscapes such as farmlands and buildings. These areas are significantly disturbed by human activities. The NPHTR has an ESP of “one screen, one district, three belts, multiple points, and multiple corridors”. BWL and YGL, which contain numerous sources and corridors, are crucial ecological functional zones. To ensure the horizontal connectivity of rare wildlife, such as of Nomascus hainanus and Cervus eldii hainanus, the NPHTR should establish buffer or development zones. These findings offer valuable insights for the development and planning of ecological civilization on Hainan Island, as well as for the establishment and management of the ESP of other national parks and nature reserves.

Background and Objectives: We aimed to investigate the carriage of colistin-resistant genes among both patients with a history of antibiotic exposure and apparently healthy adults with no recent healthcare contact. Materials and Methods: Stool swabs were collected from healthy people, and specimens were collected at the infection foci from the patients. Eleven primer/probe sets were used to perform the Multiplex Real-Time PCR assay with the QuantiNova Multiplex Probe PCR kit for screening the carriage of colistin-resistant genes (mcr-1 to mcr-10) and 16S rRNA gene as internal control. Results: In total, 86 patients and 96 healthy residents were included. Twenty two patients (25.9%) were positive with at least one colistin-resistance encoding gene. The mcr-1 gene was the most frequent (16.5%), followed by mcr-9, mcr-6, and mcr-4 genes, where the prevalence was 11.8%, 10.6%, and 9.4%, respectively. No patient was positive with mcr-3, mcr-7, and mcr-8 genes. Eight patients (9.4%) were positive with multiple colistin-encoding genes. Twenty-three healthy people (24.0%) were positive with at least one colistin-resistance encoding gene, and the mcr-10 gene was the most frequent (27.0%), followed by the mcr-1, mcr-8, and mcr-9 genes, where the prevalence was 24.3%, 21.6%, and 13.5%, respectively. No person was positive with the mcr-2 and mcr-5 genes. Conclusions: Our findings underscore the urgent need for enhanced surveillance, infection control measures, and stewardship interventions to mitigate the spread of colistin resistance in Vietnam.

Antimicrobial resistance is one of the major public health problems worldwide. This study aimed to detect the presence of extended-spectrum β-lactamase-(ESBL-)producing Escherichia (E.) coli in chicken meat in Istanbul, Türkiye. Raw chicken meat samples (n = 208) were collected from different sale points and analyzed for ESBL-producing E. coli. In total, 101 (48.5%) isolates were confirmed as E. coli by PCR, of which 80/101 (79.2%) demonstrated multiple antibiotic resistance. Resistance against amoxicillin-clavulanic acid was most frequent (87.1%). Eighteen isolates (17.8%) demonstrated phenotypical ESBL resistance, as assessed by the double disc synergy test (DDST). Isolates were tested for the presence of β-lactamase genes and mobilized colistin-resistant genes. The blaTEM group was most frequently detected (97.02%), followed by blaCTX m (45.5%), blaSHV (9.9%), and blaOXA-2 (0.9%). However, mcr genes and blaNDM, blaKPC, blaVIM, and blaOXA-48 genes were not found in any isolate. E. coli strains were tested for biofilm formation in six different media [Nutrient broth, LB broth, Tryptone Soya broth (TSB), TSB containing 1% sucrose, TSB containing 0.6% yeast extract, and BHI]. Biofilm formation by E. coli isolates (44/101, 43.5%) was highest in TSB with 1% sucrose. It is worth noting that all biofilm-producing isolates were found to harbor the blaTEM-1 gene, which can indicate a high level of antibiotic resistance. This is the first report about ESBL-producing E. coli in poultry meat, the exposure of consumers in Istanbul metropolitan areas, and the ability of E. coli from this region to produce biofilms.

The global rise in antibiotic resistance in bacteria poses a major challenge in treating infectious diseases. Polymyxins (e.g., polymyxin B and colistin) are last-resort antibiotics against resistant Gram-negative bacteria, but the effectiveness of polymyxins is decreasing due to widespread resistance among clinical isolates. The aim of this literature review was to decipher the evolving mechanisms of resistance to polymyxins among pathogens of clinical significance. We deciphered the molecular determinants of polymyxin resistance, including distinct intrinsic molecular pathways of resistance as well as evolutionary characteristics of mobile colistin resistance. Among clinical isolates, Acinetobacter stains represent a diversified evolution of resistance, with distinct molecular mechanisms of intrinsic resistance including naxD, lpxACD, and stkR gene deletion. On the other hand, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa are usually resistant via the PhoP-PhoQ and PmrA-PmrB pathways. Molecular evolutionary analysis of mcr genes was undertaken to show relative relatedness across the ten main lineages. Understanding the molecular determinants of resistance to polymyxins may help develop suitable and effective methods for detecting polymyxin resistance determinants and the development of novel antimicrobial molecules.

Antibiotic resistance caused by multidrug-resistant (MDR) bacteria is a major challenge to global public health. Polymyxins are increasingly being used as last-in-line antibiotics to treat MDR Gram-negative bacterial infections, but resistance development renders them ineffective for empirical therapy. The main mechanism that bacteria use to defend against polymyxins is to modify the lipid A headgroups of the outer membrane by adding phosphoethanolamine (PEA) moieties. In addition to lipid A modifying PEA transferases, Gram-negative bacteria possess PEA transferases that decorate proteins and glycans. This review provides a comprehensive overview of the function, structure, and mechanism of action of PEA transferases identified in pathogenic Gram-negative bacteria. It also summarizes the current drug development progress targeting this enzyme family, which could reverse antibiotic resistance to polymyxins to restore their utility in empiric therapy.

The co-existence of the colistin resistance (mcr) gene with multiple drug-resistance genes has raised concerns about the possibility of the development of pan-drug-resistant bacteria that will complicate treatment. This study aimed to investigate the antibiotic resistance profiles and co-existence of antibiotic resistance genes among the colistin-resistant Enterobacteriaceae isolates recovered from poultry and poultry meats. The antibiotic susceptibility to various classes of antibiotics was performed using the Kirby-Bauer disk diffusion method and selected antimicrobial resistance genes were detected using PCR in a total of 54 colistin-resistant Enterobacteriaceae isolates including Escherichia coli (E. coli) (n = 32), Salmonella spp. (n = 16) and Klebsiella pneumoniae (K. pneumoniae) (n = 6) isolates. Most of the isolates had multi-drug resistance (MDR), with antibiotic resistance against up to seven classes of antibiotics. All mcr-harbouring, colistin-resistant Enterobacteriaceae isolates showed this MDR (100%) phenotype. The mcr-1 harbouring E. coli isolates were co-harbouring multiple antibiotic resistance genes. The seven most commonly identified resistance genes (blaTEM, tetA, floR, aac-3-IV, aadA1, fosA, aac(6_)-lb) were detected in an mcr-1-harbouring E. coli isolate recovered from a cloacal swab. The mcr-5 harbouring Salmonella spp. isolate recovered from poultry meats was positive for blaTEM, tetA, floR, aac-3-IV, fosA and aac(6_)-lb genes. In conclusion, the colistin-resistant Enterobacteriaceae with mcr genes co-existing multiple clinically important antimicrobial resistance genes in poultry and poultry meats may cause potential future threats to infection treatment choices in humans and animals.

Acinetobacter baumannii is recognized as a clinically significant pathogen causing a wide spectrum of nosocomial infections. Colistin was considered a last-resort antibiotic for the treatment of infections caused by multidrug-resistant A. baumannii. Since the reintroduction of colistin, a number of mechanisms of colistin resistance in A. baumannii have been reported, including complete loss of LPS by inactivation of the biosynthetic pathway, modifications of target LPS driven by the addition of phosphoethanolamine (PEtN) moieties to lipid A mediated by the chromosomal pmrCAB operon and eptA gene-encoded enzymes or plasmid-encoded mcr genes and efflux of colistin from the cell. In addition to resistance to colistin, widespread heteroresistance is another feature of A. baumannii that leads to colistin treatment failure. This review aims to present a critical assessment of relevant published (>50 experimental papers) up-to-date knowledge on the molecular mechanisms of colistin resistance in A. baumannii with a detailed review of implicated mutations and the global distribution of colistin-resistant strains.

Antimicrobial resistance (AMR) is considered a serious problem in many countries, including Thailand. AMR and antibiotic resistance genes (ARGs) could transfer between humans, animals, and the environment causing a threat to human health. This study described the antibiotic resistance of Escherichia coli (E. coli) from surface water, wastewater, and discharge water in the Namsuay watershed in upper northeast Thailand. The water samples were collected in the dry and wet seasons. The 113 E. coli isolates were confirmed using a polymerase chain reaction and examined for their antibiotic susceptibility, ARGs, and genetic relationship. The results indicated that E. coli was resistant to the following classes of antibiotics: fluoroquinolone, third-generation cephalosporin, polymyxin, and carbapenem. The isolates carried the mcr-1, mcr-8, mcr-9, blaoxa-48-like, aac(6′)-bl-cr, qepA, and oqxAB genes. Phylogroup B1 was a predominant group among the E. coli in the study. In addition, the E. coli isolates from the discharge water (a hospital and a fish farm) had a higher prevalence of antibiotic resistance and harboured more ARGs than the other water sample sources. The presence of antibiotic-resistant E. coli and ARG contamination in the natural water source reflected an AMR management issue that could drive strategic policy regarding the active surveillance and prevention of AMR contamination.

Colistin is an important antimicrobial agent in the treatment of infections caused by multidrug resistant (MDR) Gram-negative bacteria. The horizontal transfer of mobile colistin resistance gene (mcr) poses a major threat to the public health worldwide. In this study, a total of thirteen mcr-carrying Escherichia coli (MCREC) strains were recovered from a tertiary hospital in Zhejiang, China, between 2016 and 2019. The minimum inhibitory concentration (MIC) of antimicrobial agents, epidemiological characteristics, and transmission dynamics of mcr-carrying isolates were analyzed using antimicrobial susceptibility testing, whole-genome sequencing, S1 nuclease pulsed-field gel electrophoresis (S1-PFGE), and southern blotting analysis. All strains were discovered to be resistant to colistin, and the majority displayed MDR phenotype. However, none of the 13 MCREC strains were resistant to carbapenems. The 13 MCREC isolates were divided into 10 different STs, including ST744, ST156, ST453, ST410, ST57, ST131, ST7034, ST2599, ST457, and ST13239, in which ST13239 was discovered for the first time. Based on core genome single nucleotide polymorphism (cgSNP) analysis, no clear epidemiological link was discovered in these strains with the exception of EC2118 and EC3807, which differ by just one SNP. A total of 35 antimicrobial resistance genes which can be divided into 14 classes were identified from the 13 MCREC isolates. According to S1-PFGE and southern blotting analyses, all 13 MCREC strains had plasmid-mediated mcr-1, and nine of them carried conjugative plasmids. In conclusion, our study revealed the emergence and dissemination of colistin-resistant E. coli isolates carrying mcr-1 in a Chinese hospital, which poses a potential risk to anti-infective therapy. More efforts should be taken to monitor the prevalence of mcr-1-carrying bacteria in China.

The establishment of ecological networks facilitates genetic exchange among species in national parks and is an effective means of avoiding habitat fragmentation. Using the proposed “Ailaoshan-Wuliangshan” in Yunnan Province, China, as the study area, the identification of ecological source sites using the morphological spatial pattern analysis (MSPA) method, extraction of potential ecological corridors using the minimum resistance model (MCR) and construction of the ecological network of national parks were performed. Based on the gravity model, important ecological corridors were selected, and corresponding ecological network optimization strategies were presented. The results showed that (1) the core area identified by MSPA was 4440.08 km2, with a low degree of fragmentation, and is distributed in strips within the woodland land classes in the study area; (2) the establishment of an ecological network model of least cost resistance based on 10 indicators in four dimensions of land tenure, geographic factors, vegetation characteristics, and human meddling; (3) the ecological network included 13 ecological source sites, 77 potential ecological corridors, 48 important ecological corridors and 25 pedestrian pathways and extracts an optimal ecological corridor connecting with the natural reserve; and (4) the network closure degree of the constructed ecological network was (1.18), line point rate (3.08), network connectivity (1.12), and cost ratio (0.98). By using the proposed ecological network construction method, ecological patches and potential corridors can be accurately identified to ensure the integrity and connectivity of the national park while minimizing the land demand pressure of the surrounding communities, which provides some reference for the construction of other national parks’ ecological networks in China.

Colistin is a last-resort drug for the treatment of infections by carbapenem-resistant Enterobacteriaceae, and the emergence of colistin resistance poses a serious clinical challenge. The aim of this study was to investigate the occurrence of colistin-resistant Escherichia coli in retail meat in Southern Italy in 2018–2020. Of 570 samples, 147 contained E. coli. Two out of 147 (1.4%) E. coli showed a non-wild-type phenotype to colistin and harboured mcr-1. mcr-1 was also detected in a wild-type isolate, resulting in a 2% mcr prevalence. mcr-1-positive isolates originated from turkey meat collected in Apulia (n = 2) and Basilicata (n = 1). A whole-genome sequencing analysis confirmed mcr-1.2 and mcr-1.1 in two and one isolate, respectively. The strains were diverse, belonging to three multi-locus sequence types (ST354, ST410, SLV of ST10) and harbouring genes mediating resistance to antimicrobials in two, six and seven classes. mcr-1 was carried by IncX4 plasmids with high nucleotide similarity to IncX4 plasmids harbouring mcr-1.2 and mcr-1.1 in Enterobacterales from different sources and geographical regions. This is the first study reporting updates on E. coli non-wild-type to colistin from retail meat in Southern Italy, highlighting the importance of phenotypic and genotypic antimicrobial resistance surveillance to contain the dissemination of mcr among E. coli.

Indane-1,3-dione is a versatile building block used in numerous applications ranging from biosensing, bioactivity, bioimaging to electronics or photopolymerization. In this review, an overview of the different chemical reactions enabling access to this scaffold but also to the most common derivatives of indane-1,3-dione are presented. Parallel to this, the different applications in which indane-1,3-dione-based structures have been used are also presented, evidencing the versatility of this structure.

Background: Antimicrobial resistance is a serious public-health problem throughout the world. Escherichia coli, the most common Gram-negative microorganism, has developed different resistance mechanisms, making treating infections difficult. Colistin is considered a last-resort drug in the treatment of infections caused by E. coli. Plasmid-mediated mobile-colistin-resistant (mcr) genes in E. coli, now disseminated globally, are considered a major public-health threat. Humans, chickens, and pigs are the main reservoirs for E. coli and the sources of antibiotic resistance. Hence, an up-to-date and precise estimate of the global prevalence of mcr resistance genes in these reservoirs is necessary to understand more precisely the worldwide spread and to more effectively implement control and prevention strategies. Methodology: Publications were identified in the PubMed database on the basis of the PRISMA guidelines. English full-text articles were selected from December 2014 to March 2021. Descriptive statistics and a meta-analysis were performed in Excel and R software, respectively. Colistin resistance was defined as the molecular-genetic detection of the mcr genes. The crude and estimated prevalence were calculated for each host and continent. The studies were divided into two groups; community-based when they involved isolates from healthy humans, chickens, or pigs, and clinical studies when they involved only hospital, outpatient, or laboratory isolates. Results: A total of 1278 studies were identified and 218 were included in this systematic review and meta-analysis, divided into community studies (159 studies) and clinical studies (59 studies). The general prevalence of mcr-mediated colistin-resistant E. coli (mcrMCRE) was 6.51% (n = 11,583/177,720), reported in 54 countries and on five continents; Asia with 119 studies followed by Europe with 61 studies registered the most articles. Asia reported the major diversity of mcr-variants (eight of nine, except mcr-2). Worldwide, chickens and pigs proved to be the principal reservoir of mcr with an estimated prevalence of 15.8% and 14.9%, respectively. Healthy humans and clinical isolates showed a lower prevalence with 7.4% and 4.2% respectively. Conclusions: In this systematic review and meta-analysis, the worldwide prevalence of mcr in E. coli isolated from healthy humans, chickens, and pigs was investigated. A wide prevalence and distribution of mcr genes was demonstrated on all continents in E. coli isolates from the selected reservoirs. Understanding the epidemiology and occurrence in the reservoirs of mcr in E. coli on different continents of the world facilitates tracing how mcr genes are transmitted and determining the infection risks for humans. This knowledge can be used to reduce the incidence of zoonotic transmission by implementing the appropriate control programs.

The evaluation of ecological risk and the construction of ecological security patterns are significant for the conservation of World Natural Heritage sites with high outstanding universal value. This paper constructed a landscape ecological risk evaluation framework for Bayinbuluke using the three aspects of the “nature–society–landscape pattern” and a cumulative resistance surface from the risk evaluation results. The ecological sources were identified based on Morphological Spatial Pattern Analysis (MSPA) and the landscape index. Finally, the Minimum Cumulative Resistance model (MCR) and gravity model were used to obtain both key ecological corridors and general ecological corridors. The results showed that: (1) the influencing factors of landscape ecological risk were, in order of strongest to weakest, landscape pattern factors, natural factors, and social factors; (2) the spatial differences in terms of landscape ecological risk within the study area could be identified. Low-risk areas were mainly concentrated in the core area, high-risk areas were mainly in the outer buffer zone, and the overall ecological risk level at Bayinbuluke was high; and (3) a total of four key corridors and ten general corridors could be constructed. This study provides a reference for decision-making on the ecological security and protection of heritage sites.

Antimicrobial resistance is one of the major public health problems worldwide. This study aimed to detect the presence of extended-spectrum β-lactamase-(ESBL-)producing Escherichia ( E. ) coli in chicken meat in Istanbul, Türkiye. Raw chicken meat samples ( n = 208) were collected from different sale points and analyzed for ESBL-producing E. coli . In total, 101 (48.5%) isolates were confirmed as E. coli by PCR, of which 80/101 (79.2%) demonstrated multiple antibiotic resistance. Resistance against amoxicillin-clavulanic acid was most frequent (87.1%). Eighteen isolates (17.8%) demonstrated phenotypical ESBL resistance, as assessed by the double disc synergy test (DDST). Isolates were tested for the presence of β-lactamase genes and mobilized colistin-resistant genes. The bla TEM group was most frequently detected (97.02%), followed by bla CTX m (45.5%), bla SHV (9.9%), and bla OXA-2 (0.9%). However, mcr genes and bla NDM, bla KPC , bla VIM , and bla OXA-48 genes were not found in any isolate. E. coli strains were tested for biofilm formation in six different media [Nutrient broth, LB broth, Tryptone Soya broth (TSB), TSB containing 1% sucrose, TSB containing 0.6% yeast extract, and BHI]. Biofilm formation by E. coli isolates (44/101, 43.5%) was highest in TSB with 1% sucrose. It is worth noting that all biofilm-producing isolates were found to harbor the bla TEM-1 gene, which can indicate a high level of antibiotic resistance. This is the first report about ESBL-producing E. coli in poultry meat, the exposure of consumers in Istanbul metropolitan areas, and the ability of E. coli from this region to produce biofilms.

Salmonellosis is one of the most important zoonoses in Europe and the world. Human infection may evolve in severe clinical diseases, with the need for hospitalization and antimicrobial treatment. Colistin is now considered an important antimicrobial to treat infections from multidrug- resistant Gram-negative bacteria, but the spreading of mobile colistin-resistance (mcr) genes has limited this option. We aimed to evaluate colistin minimum inhibitory concentration and the presence of mcr (mcr-1 to mcr-9) genes in 236 Salmonella isolates previously collected from different animals and the environment between 2000 and 2020. Overall, 17.79% of isolates were resistant to colistin; no differences were observed in relation to years of isolation (2000–2005, 2009–2014, and 2015–2020), Salmonella enterica subspecies (enterica, salamae, diarizonae, and houtenae), origin of samples (domestic animals, wildlife, and environment), or animal category (birds, mammals, and reptiles); only recently isolated strains from houseflies showed the most resistance. Few isolates (5.93%) scored positive for mcr genes, in particular for mcr-1, mcr-2, mcr-4, mcr-6, and mcr-8; furthermore, only 2.54% of isolates were mcr-positive and colistin-resistant. Detected resistance to colistin was equally distributed among all examined Salmonella isolates and not always related to the presence of mcr genes.

Open-cast coal mining in China has developed rapidly due to its obvious advantages over underground mining. However, it may have negative ecological effects, such as biodiversity loss, water shortage, and soil erosion. Identifying and protecting the key areas with high importance for ecological sustainability are great challenges. The construction of an ecological security pattern (ESP) can improve landscape connectivity and reduce the fragmentation of ecological patches. Thus, it can be seen as an effective measure to protect regional ecological sustainability. In this study, taking the Pingshuo open-cast mining area as a case study area, ecological sources are identified through ecosystem structure and function, and corridors are extracted by constructing an ecological resistance surface, thus forming a valid ecological network. The results show that in 2018, the ESP in the study area included 11 sources with an area of 147.74 km2 and 17 corridors with a length of 92.11 km. Specifically, the ecological sources are mainly distributed in Taocun Township, Jingping Township, and Xiangyangbao Township. Among these 11 sources, sources 7 and 8 are reclaimed waste dump land, meaning that the land reclamation work in Pingshuo greatly promotes connectivity. Furthermore, dump 1 can be restored in the future by constructing three new corridors, which will greatly improve the landscape connectivity of Yuling Township. Overall, this study not only provides an effective framework for constructing and optimizing ESPs in ecologically fragile coal mining areas, but it also adds new insights to the concept of land reclamation in these areas.

Background: A collection of human-epidemiologically unrelated S. enterica strains collected over a 3-year period (2016 to 2018) in Italy by the national surveillance Enter-Net Italia was analysed. Methods: Antimicrobial susceptibility tests, including the determination of minimal inhibitory concentrations (MICs) for colistin, were performed. Colistin resistant strains were analysed by PCR to detect mobile colistin resistance (mcr) genes. In mcr-negative S. enterica serovar Enteritidis strains, chromosomal mutations potentially involved in colistin resistance were identified by a genomic approach. Results: The prevalence of colistin-resistant S. enterica strains was 7.7%, the majority (87.5%) were S. Enteritidis. mcr genes were identified only in one strain, a S. Typhimurium monophasic variant, positive for both mcr-1.1 and mcr-5.1 genes in an IncHI2 ST4 plasmid. Several chromosomal mutations were identified in the colistin-resistant mcr-negative S. Enteritidis strains in proteins involved in lipopolysaccharide and outer membrane synthesis and modification (RfbN, LolB, ZraR) and in a component of a multidrug efflux pump (MdsC). These mutated proteins were defined as possible candidates for colistin resistance in mcr-negative S. Enteritidis of our collection. Conclusions: The colistin national surveillance in Salmonella spp. in humans, implemented with genomic-based surveillance, permitted to monitor colistin resistance, determining the prevalence of mcr determinants and the study of new candidate mechanisms for colistin resistance.

The emergence of mobile colistin resistance (mcr)-mediated polymyxin resistance has resulted in a significant detriment to the utility of the polymyxins in the clinical setting. Though the risk for horizontal transfer of an mcr-containing plasmid is a major component of the transmissibility, selection of polymyxin resistant subpopulations is still a major risk factor for developing polymyxin-resistant infections. Using static time-kills over 24 h (h), we performed competition studies by mixing known inocula of isogenic Escherichia coli strains (wildtype [WT] and mcr-1-harboring) and treating with a concentration array of polymyxin B. These results were then compared to a priori predictions of bacterial-killing effects by polymyxin B on a mixed population of E. coli cells using a previously published mechanism-based model. The data showed that both selective pressure between WT and mcr-1-harboring strains as well as underlying polymyxin B heteroresistance within each of the two strains contributed to bacterial regrowth despite treatment with high concentration polymyxin B. Moreover, the simulations showed that when mcr-1-harboring cells were 1% or 10% of the total population, regrowth by 24 h was still observed in ≥50% of the simulated subjects for both a 106 and 108 inoculum. These results indicate that at lower inoculums with a low proportion of mcr-1-harboring cells, selective pressure from a pharmacokinetic-optimized regimen of polymyxin B still results in regrowth and selection of polymyxin-resistant cells.

The objective of this review is to collect and present the results of relevant studies on an international level, on the subject of colistin resistance due to mcr genes prevalence in livestock animals. After a literature search, and using PRISMA guidelines principles, a total of 40 swine, 16 bovine and 31 poultry studies were collected concerning mcr-1 gene; five swine, three bovine and three poultry studies referred to mcr-2 gene; eight swine, one bovine, two poultry studies were about mcr-3 gene; six swine, one bovine and one poultry manuscript studied mcr-4 gene; five swine manuscripts studied mcr-5 gene; one swine manuscript was about mcr-6, mcr-7, mcr-8, mcr-9 genes and one poultry study about mcr-10 gene was found. Information about colistin resistance in bacteria derived from animals and animal product foods is still considered limited and that should be continually enhanced; most of the information about clinical isolates are relative to enteropathogens Escherichia coli and Salmonella spp. This review demonstrates the widespread dispersion of mcr genes to livestock animals, indicating the need to further increase measures to control this important threat for public health issue.

Dissemination of the mobile colistin resistance gene mcr in Enterobacterales among humans, animals, and the environment is a public health issue. We characterized mcr genes in the Klebsiella pneumoniae complex (KpnC) isolated from slaughtered pigs in Thailand. The 280 KpnCs consisted of K. pneumoniae (85%), Klebsiella quasipneumoniae (8.21%), and Klebsiella variicola (6.79%). mcr genes were detected in 6.79% (19/280) of KpnC isolates, consisting of mcr-8 (n = 9; 3.21%), mcr-7 (n = 7; 2.50%), mcr-7 + mcr-8 (n = 2; 0.71%), and mcr-1 + mcr-7 (n = 1; 0.36%). K. pneumoniae predominantly carried the mcr-7 and mcr-8 genes, while K. variicola and K. quasipneumoniae harbored mcr-7 and mcr-8, respectively. Six of the nineteen mcr-harboring KpnC isolates exhibited colistin resistance, and five had mcr-1 or mcr-8 transferable to an Escherichia coli recipient. Antimicrobial susceptibility analysis revealed that all mcr-carrying KpnC isolates were susceptible to carbapenems, cefotaxime, cefepime, amoxicillin/clavulanic acid, piperacillin/tazobactam, amikacin, and fosfomycin, and had high resistance to azithromycin. Multilocus sequence analysis demonstrated that the mcr-harboring KpnC isolates were genetically diverse. A ‘One-Health’ approach is useful to combat antimicrobial-resistant bacteria through coordinating the human, animal, and environmental sectors. Hence, continuous monitoring and surveillance of mcr-carrying KpnCs throughout the pork supply chain is crucial for ensuring public health.

The aim of this study was continuous monitoring of the presence of mcr-1 to mcr-5 genes in Enterobacterales isolated from cattle, pigs, and domestic poultry at intensive breeding facilities in Northern Vojvodina, Serbia, from 1 January 1 to 1 October 2020. Out of 2167 examined samples, mcr-1 was observed in five E. coli isolates originating from healthy turkeys. Four isolates belonged to the phylogenetic group B1, and one isolate to the phylogenetic group A. Detected E. coli serogenotypes (somatic O and flagellar H antigens) were O8:H25 and O29:H25. Core-genome multi-locus sequence typing (cgMLST) revealed three ST58 isolates clustering together in Clonal Complex (CC) 155 and two singletons of ST641-CC86 and ST410-CC23, respectively. Clonotyping revealed CH4-32 (n = 3), CH6-53 (n = 1) and CH4-24 (n = 1). In all isolates, the mcr-1 gene was located on a large IncX4 replicon type plasmid. Eight virulence-associated genes (VAGs) typical of avian pathogenic E. coli (APEC) (fyuA, fimH, hlyF, iss, ompT, sitA, traT, iroN) were detected in four isolates. These isolates were investigated for susceptibility to four biocides and revealed MIC values of 0.125% for glutardialdehyde, of 0.00003–0.00006% for chlorohexidine, of 4–6% for isopropanol and of 0.001–0.002% for benzalkonium chloride. All obtained MIC values of the tested biocides were comparable to the reference strain, with no indication of possible resistance. This is the first report of mcr-1.1-carrying E. coli from Serbia. Although only samples from turkeys were mcr-positive in this study, continuous monitoring of livestock samples is advised to prevent a spill-over from animals to humans.

Background: In order to estimate the prevalence of plasmid borne colistin resistance and to characterize in detail the mcr-positive isolates, we carried out a sentinel testing survey on the intestinal carriage of plasmid-mediated colistin-resistant Enterobacteriaceae in hospitalized patients. Methods: Between June 2018 and September 2019, 1922 faecal samples from hospitalised patients were analysed by selective culture in presence of colistin (3.5 mg/L), and in parallel by direct detection of the mcr-1 to mcr-8 genes by qPCR. The mcr-positive isolates were characterised by whole-genome sequencing. Results: The prevalence of the mcr-1 gene was 0.21% (n = 4/1922); the mcr-2 to 8 genes were not detected. The mcr-1 gene was found to be localised in the IncX4 (n = 3) and IncHI2 (n = 1) plasmid type. One Escherichia coli isolate was susceptible to colistin due to the inactivation of the mcr-1 gene through the insertion of the IS2 element; however, the colistin resistance was inducible by culture in low concentrations of colistin. One human mcr-1 positive E. coli isolate was related genetically to the mcr-1 E. coli isolate derived from turkey meat of Czech origin. Conclusions:mcr-mediated colistin resistance currently poses little threat to patients hospitalised in Czech healthcare settings. The presence of the mcr-1 gene in the human population has a possible link to domestically produced, retail meat.

Colistin use has mostly been stopped in human medicine, due to its toxicity. However, nowadays, it still is used as a last-resort antibiotic to treat hospital infections caused by multi-drug resistant Enterobacteriaceae. On the contrary, colistin has been used in veterinary medicine until recently. In this study, 210 fecal samples from pigs (n = 57), calves (n = 152), and the farmer (n = 1) were collected from a farm where E. coli harboring mcr-1–mcr-3 was previously detected. Samples were plated, and mcr-genes presence was confirmed by multiplex-PCR. Hybrid sequencing which determined the presence and location of mcr-1, other antibiotic resistance genes, and virulence factors. Eighteen colistin resistant isolates (13 from calves, four from pigs, and one from the farmer) contained mcr-1 associated with plasmids (IncX4, IncI2, and IncHI2), except for two that yielded mcr-1 in the chromosome. Similar plasmids were distributed in different E. coli lineages. Transmission of mcr-1 to the farmer most likely occurred by horizontal gene transfer from E. coli of calf origin, since plasmids were highly similar (99% coverage, 99.97% identity). Moreover, 33 virulence factors, including stx2 for Shiga toxin E. coli (STEC) were detected, highlighting the role of livestock as a reservoir of pathotypes with zoonotic potential.

Antibiotic resistance has become a global public health concern. To determine the distribution characteristics of mcr and blaNDM in China, gene screening was conducted directly from gut specimens sourced from livestock and poultry, poultry environments, human diarrhea patients, and wild animals from 10 regions, between 2010–2020. The positive rate was 5.09% (356/6991) for mcr and 0.41% (29/6991) for blaNDM, as detected in gut specimens from seven regions, throughout 2010 to 2019, but not detected in 2020. The detection rate of mcr showed significant differences among various sources: livestock and poultry (14.81%) > diarrhea patients (1.43%) > wild animals (0.36%). The detection rate of blaNDM was also higher in livestock and poultry (0.88%) than in diarrhea patients (0.17%), and this was undetected in wildlife. This is consistent with the relatively high detection rate of multiple mcr genotypes in livestock and poultry. All instances of coexistence of the mcr-1 and blaNDM genes, as well as coexistence of mcr genotypes within single specimens, and most new mcr subtypes came from livestock, and poultry environments. Our study indicates that the emergence of mcr and blaNDM genes in China is closely related to the selective pressure of carbapenem and polymyxin. The gene-based strategy is proposed to identify more resistance genes of concern, possibly providing guidance for the prevention and control of antimicrobial resistance dissemination.

Four colistin susceptibility testing methods were compared with the standard broth microdilution (BMD) in a collection of 75 colistin-susceptible and 75 mcr-positive E. coli, including ST131 isolates. Taking BMD as reference, all methods showed similar categorical agreement rates (CA) of circa 90%, and a low number of very major errors (VME) (0% for the MicroScan system and Etest®, 0.7% for UMIC®), except for the disc diffusion assay (breakpoint ≤ 11 mm), which yielded false-susceptible results for 8% of isolates. Of note is the number of mcr-positive isolates (17.3%) categorized as susceptible (≤2 mg/L) by the BMD method, but as resistant by the MicroScan system. ST131 mcr-positive E. coli were identified as colistin-resistant by all MIC-based methods. Our results show that applying the current clinical cut-off (>2 mg/L), many mcr-positive E. coli remain undetected, while applying a threshold of >1 mg/L the sensitivity of detection increases significantly without loss of specificity. We propose two possible workflows, both starting with the MicroScan system, since it is automated and, importantly, it categorized all mcr-positive isolates as colistin-resistant. MicroScan should be followed by either BMD or MIC-based commercial methods for colistin resistance detection; or, alternatively, MicroScan, followed by PCR for the mcr screening.

The resistance of Gram-negative bacteria to colistin, mediated by plasmid-borne mcr genes, is an emerging public health concern. The complete genome sequence (4.55 Mb) of a clinical isolate of Aeromonas veronii biovar veronii obtained from a patient with septicemia was determined using short-read and long-read platforms. This isolate (C198) was found to harbor a novel mcr-3 gene, designated mcr-3.41. Isolate C198 revealed adjacent mcr-3.41 and mcr-3-like genes. It contained one chromosome and two plasmids, both of which encoded a RepB replication protein. Other antimicrobial resistance genes, including blacphA3, blaOXA-12, tetA, rsmA, and adeF, were also present. Isolate C198 was resistant to amoxicillin–clavulanate, ampicillin–sulbactam and tetracycline, and showed intermediate resistance to trimethoprim–sulfamethoxazole. The isolate was susceptible to piperacillin–tazobactam, carbapenem, third-generation cephalosporins, fluoroquinolones, chloramphenicol, and aminoglycosides. Putative virulence genes in the C198 genome encoded type II, III, and VI secretion systems; type IV Aeromonas pili; and type I fimbria, flagella, hemagglutinin, aerolysin, and hemolysins. Multilocus sequence typing revealed a novel sequence type (ST), ST720 for C198. Phylogenetic analysis of the single nucleotide polymorphisms in C198 demonstrated that the strain was closely related to A. veronii 17ISAe. The present study provides insights into the genomic characteristics of human A. veronii isolates.

Following their initial discovery in the 1940s, polymyxin antibiotics fell into disfavor due to their potential clinical toxicity, especially nephrotoxicity. However, the dry antibiotic development pipeline, together with the rising global prevalence of infections caused by multidrug-resistant (MDR) Gram-negative bacteria have both rejuvenated clinical interest in these polypeptide antibiotics. Parallel to the revival of their use, investigations into the mechanisms of action and resistance to polymyxins have intensified. With an initial known effect on biological membranes, research has uncovered the detailed molecular and chemical interactions that polymyxins have with Gram-negative outer membranes and lipopolysaccharide structure. In addition, genetic and epidemiological studies have revealed the basis of resistance to these agents. Nowadays, resistance to polymyxins in MDR Gram-negative pathogens is well elucidated, with chromosomal as well as plasmid-encoded, transferrable pathways. The aims of the current review are to highlight the important chemical, microbiological, and pharmacological properties of polymyxins, to discuss their mechanistic effects on bacterial membranes, and to revise the current knowledge about Gram-negative acquired resistance to these agents. Finally, recent research, directed towards new perspectives for improving these old agents utilized in the 21st century, to combat drug-resistant pathogens, is summarized.

X-ray absorption spectroscopy (XAS) today represents a widespread and powerful technique, able to monitor complex systems under in situ and operando conditions, while external variables, such us sampling time, sample temperature or even beam position over the analysed sample, are varied. X-ray absorption spectroscopy is an element-selective but bulk-averaging technique. Each measured XAS spectrum can be seen as an average signal arising from all the absorber-containing species/configurations present in the sample under study. The acquired XAS data are thus represented by a spectroscopic mixture composed of superimposed spectral profiles associated to well-defined components, characterised by concentration values evolving in the course of the experiment. The decomposition of an experimental XAS dataset in a set of pure spectral and concentration values is a typical example of an inverse problem and it goes, usually, under the name of multivariate curve resolution (MCR). In the present work, we present an overview on the major techniques developed to realize the MCR decomposition together with a selection of related results, with an emphasis on applications in catalysis. Therein, we will highlight the great potential of these methods which are imposing as an essential tool for quantitative analysis of large XAS datasets as well as the directions for further development in synergy with the continuous instrumental progresses at synchrotron sources.

Colistin, a last-resort antibiotic, has been used in controlling infections caused by multidrug-resistant Gram-negative bacterial pathogens. However, recent reports showed a global dissemination of mobile colistin-resistance (mcr) genes, genetic elements that encode resistance to colistin, which has raised public health concerns. These mcr genes threaten the effectiveness of colistin and could limit therapy options for complicated infections. Despite global attention, many facets of the molecular epidemiology of mcr remain poorly characterized. Here, we focus on the role of travel and the international food trade in the dissemination of mcr to countries where these genetic elements and/or colistin resistance are relatively limited in prevalence. We present evidence from the literature on the acquisition of mcr during travel, and the carriage of these genes back to travelers’ countries. We also highlight the potential transmission of mcr via imported foods. These observations emphasize the magnitude of efforts that are needed to control the spread of mcr, and further highlight the challenge of antimicrobial resistance and the urgent need for coordinated global action.

Ionic liquids (ILs) are a convenient and inexpensive source of N-heterocyclic carbenes (NHCs). In this study, dialkyl imidazolium-based ILs are used as carbene precursors in a four-component synthesis of oxo triphenylhexanoates (OTHOs), where it was found that IL outperformed commonly used NHC precatalysts in terms of reaction efficiency. The reaction is highly stereoselective, delivering the anti-diastereomer (20:1 dr), and the OTHOs can be obtained in high-to-excellent yields. By virtue of the four-component reaction-setup, facile construction of the OTHO scaffold with a diverse set of functional groups (21 examples) can be achieved. In the context of sustainability, the IL can be recovered and reused several times without affecting selectivity or yield. Moreover, most compounds can be isolated by precipitation and filtration, mitigating the use of solvent-demanding chromatography.

The global rise in antibiotic resistance in bacteria poses a major challenge in treating infectious diseases. Polymyxins (e.g., polymyxin B and colistin) are last-resort antibiotics against resistant Gram-negative bacteria, but the effectiveness of polymyxins is decreasing due to widespread resistance among clinical isolates. The aim of this literature review was to decipher the evolving mechanisms of resistance to polymyxins among pathogens of clinical significance. We deciphered the molecular determinants of polymyxin resistance, including distinct intrinsic molecular pathways of resistance as well as evolutionary characteristics of mobile colistin resistance. Among clinical isolates, Acinetobacter stains represent a diversified evolution of resistance, with distinct molecular mechanisms of intrinsic resistance including nax D, lpx ACD, and stk R gene deletion. On the other hand, Escherichia coli , Klebsiella pneumoniae , and Pseudomonas aeruginosa are usually resistant via the PhoP-PhoQ and PmrA-PmrB pathways. Molecular evolutionary analysis of mcr genes was undertaken to show relative relatedness across the ten main lineages. Understanding the molecular determinants of resistance to polymyxins may help develop suitable and effective methods for detecting polymyxin resistance determinants and the development of novel antimicrobial molecules.

Colistin is widely used in food-animal production. Salmonella enterica is a zoonotic pathogen, which can pass from animal to human microbiota through the consumption of contaminated food, and cause disease, often severe, especially in young children, elderly and immunocompromised individuals. Recently, plasmid-mediated colistin resistance was recognised; mcr-like genes are being identified worldwide. Colistin is not an antibiotic used to treat Salmonella infections, but has been increasingly used as one of the last treatment options for carbapenem resistant Enterobacteria in human infections. The finding of mobilizable mcr-like genes became a global concern due to the possibility of horizontal transfer of the plasmid that often carry resistance determinants to beta-lactams and/or quinolones. An understanding of the origin and dissemination of mcr-like genes in zoonotic pathogens such as S. enterica will facilitate the management of colistin use and target interventions to prevent further spread. The main objective of this review was to collect epidemiological data about mobilized colistin resistance in S. enterica, describing the mcr variants, identified serovars, origin of the isolate, country and other resistance genes located in the same genetic platform.

Antibiotic resistance caused by multidrug-resistant (MDR) bacteria is a major challenge to global public health. Polymyxins are increasingly being used as last-in-line antibiotics to treat MDR Gram-negative bacterial infections, but resistance development renders them ineffective for empirical therapy. The main mechanism that bacteria use to defend against polymyxins is to modify the lipid A headgroups of the outer membrane by adding phosphoethanolamine (PEA) moieties. In addition to lipid A modifying PEA transferases, Gram-negative bacteria possess PEA transferases that decorate proteins and glycans. This review provides a comprehensive overview of the function, structure, and mechanism of action of PEA transferases identified in pathogenic Gram-negative bacteria. It also summarizes the current drug development progress targeting this enzyme family, which could reverse antibiotic resistance to polymyxins to restore their utility in empiric therapy.

The co-existence of the colistin resistance ( mcr ) gene with multiple drug-resistance genes has raised concerns about the possibility of the development of pan-drug-resistant bacteria that will complicate treatment. This study aimed to investigate the antibiotic resistance profiles and co-existence of antibiotic resistance genes among the colistin-resistant Enterobacteriaceae isolates recovered from poultry and poultry meats. The antibiotic susceptibility to various classes of antibiotics was performed using the Kirby-Bauer disk diffusion method and selected antimicrobial resistance genes were detected using PCR in a total of 54 colistin-resistant Enterobacteriaceae isolates including Escherichia coli ( E . coli ) (n = 32), Salmonella spp. (n = 16) and Klebsiella pneumoniae ( K . pneumoniae ) (n = 6) isolates. Most of the isolates had multi-drug resistance (MDR), with antibiotic resistance against up to seven classes of antibiotics. All mcr -harbouring, colistin-resistant Enterobacteriaceae isolates showed this MDR (100%) phenotype. The mcr-1 harbouring E . coli isolates were co-harbouring multiple antibiotic resistance genes. The seven most commonly identified resistance genes ( bla TEM , tetA , floR , aac-3-IV , aadA1 , fosA , aac ( 6_ ) -lb ) were detected in an mcr-1 -harbouring E . coli isolate recovered from a cloacal swab. The mcr-5 harbouring Salmonella spp. isolate recovered from poultry meats was positive for bla TEM , tetA , floR , aac-3-IV , fosA and aac ( 6_ ) -lb genes. In conclusion, the colistin-resistant Enterobacteriaceae with mcr genes co-existing multiple clinically important antimicrobial resistance genes in poultry and poultry meats may cause potential future threats to infection treatment choices in humans and animals.

The title compound was synthesized by multicomponent condensation of 3-amino-1,2,4-triazole, acetone and 5-bromo-2-hydroxy-3-methoxybenzaldehyde. The structure was established by 1H-NMR, 13C-NMR, IR spectroscopy and LC-MS.

A collection of smart multicomponent reactions (MCRs) with continuative post condensation cyclizations (PCCs) is presented to construct conventional three- to seven-membered heterocyclic compounds in diversity oriented syntheses (DOS). These will provide a high degree of applying economical and ecological advantages as well as of practicability. Water, ionic liquids, and solvent-less syntheses as well as use of various forms of energy as microwave and ultrasonic irradiation are examined and discussed.

Acinetobacter baumannii is recognized as a clinically significant pathogen causing a wide spectrum of nosocomial infections. Colistin was considered a last-resort antibiotic for the treatment of infections caused by multidrug-resistant A. baumannii . Since the reintroduction of colistin, a number of mechanisms of colistin resistance in A. baumannii have been reported, including complete loss of LPS by inactivation of the biosynthetic pathway, modifications of target LPS driven by the addition of phosphoethanolamine (PEtN) moieties to lipid A mediated by the chromosomal pmrCAB operon and eptA gene-encoded enzymes or plasmid-encoded mcr genes and efflux of colistin from the cell. In addition to resistance to colistin, widespread heteroresistance is another feature of A. baumannii that leads to colistin treatment failure. This review aims to present a critical assessment of relevant published (>50 experimental papers) up-to-date knowledge on the molecular mechanisms of colistin resistance in A. baumannii with a detailed review of implicated mutations and the global distribution of colistin-resistant strains.

Antimicrobial agents are used in both veterinary and human medicine. The intensive use of antimicrobials in animals may promote the fixation of antimicrobial resistance genes in bacteria, which may be zoonotic or capable to transfer these genes to human-adapted pathogens or to human gut microbiota via direct contact, food or the environment. This review summarizes the current knowledge of the use of antimicrobial agents in animal health and explores the role of bacteria from animals as a pool of antimicrobial resistance genes for human bacteria. This review focused in relevant examples within the ESC(K)APE (Enterococcus faecium, Staphylococcus aureus, Clostridium difficile (Klebsiella pneumoniae), Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacteriaceae) group of bacterial pathogens that are the leading cause of nosocomial infections throughout the world.

Several novel methods, catalysts and reagents have been developed to improve organic synthesis. Synergistic effects between reactions, reagents and catalysts can lead to minor heats of reaction and occur as an inherent result of multicomponent reactions (MCRs) and their extensions. They enable syntheses to be performed at a low energy level and the number of synthesis steps to be drastically reduced in comparison with ‘classical’ two-component reactions, fulfilling the rules of Green Chemistry. The very high potential for variability, diversity and complexity of MCRs additionally generates an extremely diverse range of products, thus bringing us closer to the aim of being able to produce tailor-made and extremely low-cost materials, drugs and compound libraries.

Antimicrobial resistance (AMR) is considered a serious problem in many countries, including Thailand. AMR and antibiotic resistance genes (ARGs) could transfer between humans, animals, and the environment causing a threat to human health. This study described the antibiotic resistance of Escherichia coli ( E. coli ) from surface water, wastewater, and discharge water in the Namsuay watershed in upper northeast Thailand. The water samples were collected in the dry and wet seasons. The 113 E. coli isolates were confirmed using a polymerase chain reaction and examined for their antibiotic susceptibility, ARGs, and genetic relationship. The results indicated that E. coli was resistant to the following classes of antibiotics: fluoroquinolone, third-generation cephalosporin, polymyxin, and carbapenem. The isolates carried the mcr-1 , mcr-8 , mcr-9 , bla oxa-48-like , aac(6')-bl-cr , qepA , and oqxAB genes. Phylogroup B1 was a predominant group among the E. coli in the study. In addition, the E. coli isolates from the discharge water (a hospital and a fish farm) had a higher prevalence of antibiotic resistance and harboured more ARGs than the other water sample sources. The presence of antibiotic-resistant E. coli and ARG contamination in the natural water source reflected an AMR management issue that could drive strategic policy regarding the active surveillance and prevention of AMR contamination.

Colistin is an important antimicrobial agent in the treatment of infections caused by multidrug resistant (MDR) Gram-negative bacteria. The horizontal transfer of mobile colistin resistance gene ( mcr ) poses a major threat to the public health worldwide. In this study, a total of thirteen mcr -carrying Escherichia coli (MCREC) strains were recovered from a tertiary hospital in Zhejiang, China, between 2016 and 2019. The minimum inhibitory concentration (MIC) of antimicrobial agents, epidemiological characteristics, and transmission dynamics of mcr -carrying isolates were analyzed using antimicrobial susceptibility testing, whole-genome sequencing, S1 nuclease pulsed-field gel electrophoresis (S1-PFGE), and southern blotting analysis. All strains were discovered to be resistant to colistin, and the majority displayed MDR phenotype. However, none of the 13 MCREC strains were resistant to carbapenems. The 13 MCREC isolates were divided into 10 different STs, including ST744, ST156, ST453, ST410, ST57, ST131, ST7034, ST2599, ST457, and ST13239, in which ST13239 was discovered for the first time. Based on core genome single nucleotide polymorphism (cgSNP) analysis, no clear epidemiological link was discovered in these strains with the exception of EC2118 and EC3807, which differ by just one SNP. A total of 35 antimicrobial resistance genes which can be divided into 14 classes were identified from the 13 MCREC isolates. According to S1-PFGE and southern blotting analyses, all 13 MCREC strains had plasmid-mediated mcr-1 , and nine of them carried conjugative plasmids. In conclusion, our study revealed the emergence and dissemination of colistin-resistant E. coli isolates carrying mcr-1 in a Chinese hospital, which poses a potential risk to anti-infective therapy. More efforts should be taken to monitor the prevalence of mcr-1 -carrying bacteria in China.

Colistin is a last-resort drug for the treatment of infections by carbapenem-resistant Enterobacteriaceae , and the emergence of colistin resistance poses a serious clinical challenge. The aim of this study was to investigate the occurrence of colistin-resistant Escherichia coli in retail meat in Southern Italy in 2018-2020. Of 570 samples, 147 contained E. coli . Two out of 147 (1.4%) E. coli showed a non-wild-type phenotype to colistin and harboured mcr-1 . mcr-1 was also detected in a wild-type isolate, resulting in a 2% mcr prevalence. mcr-1 -positive isolates originated from turkey meat collected in Apulia (n = 2) and Basilicata (n = 1). A whole-genome sequencing analysis confirmed mcr-1.2 and mcr-1.1 in two and one isolate, respectively. The strains were diverse, belonging to three multi-locus sequence types (ST354, ST410, SLV of ST10) and harbouring genes mediating resistance to antimicrobials in two, six and seven classes. mcr-1 was carried by IncX4 plasmids with high nucleotide similarity to IncX4 plasmids harbouring mcr-1.2 and mcr-1.1 in Enterobacterales from different sources and geographical regions. This is the first study reporting updates on E. coli non-wild-type to colistin from retail meat in Southern Italy, highlighting the importance of phenotypic and genotypic antimicrobial resistance surveillance to contain the dissemination of mcr among E. coli .

Background: Antimicrobial resistance is a serious public-health problem throughout the world. Escherichia coli , the most common Gram-negative microorganism, has developed different resistance mechanisms, making treating infections difficult. Colistin is considered a last-resort drug in the treatment of infections caused by E. coli . Plasmid-mediated mobile-colistin-resistant ( mcr ) genes in E. coli , now disseminated globally, are considered a major public-health threat. Humans, chickens, and pigs are the main reservoirs for E. coli and the sources of antibiotic resistance. Hence, an up-to-date and precise estimate of the global prevalence of mcr resistance genes in these reservoirs is necessary to understand more precisely the worldwide spread and to more effectively implement control and prevention strategies. Methodology : Publications were identified in the PubMed database on the basis of the PRISMA guidelines. English full-text articles were selected from December 2014 to March 2021. Descriptive statistics and a meta-analysis were performed in Excel and R software, respectively. Colistin resistance was defined as the molecular-genetic detection of the mcr genes. The crude and estimated prevalence were calculated for each host and continent. The studies were divided into two groups; community-based when they involved isolates from healthy humans, chickens, or pigs, and clinical studies when they involved only hospital, outpatient, or laboratory isolates. Results : A total of 1278 studies were identified and 218 were included in this systematic review and meta-analysis, divided into community studies (159 studies) and clinical studies (59 studies). The general prevalence of mcr -mediated colistin-resistant E. coli ( mcrMCRE ) was 6.51% (n = 11,583/177,720), reported in 54 countries and on five continents; Asia with 119 studies followed by Europe with 61 studies registered the most articles. Asia reported the major diversity of mcr -variants (eight of nine, except mcr-2 ). Worldwide, chickens and pigs proved to be the principal reservoir of mcr with an estimated prevalence of 15.8% and 14.9%, respectively. Healthy humans and clinical isolates showed a lower prevalence with 7.4% and 4.2% respectively. Conclusions : In this systematic review and meta-analysis, the worldwide prevalence of mcr in E. coli isolated from healthy humans, chickens, and pigs was investigated. A wide prevalence and distribution of mcr genes was demonstrated on all continents in E. coli isolates from the selected reservoirs. Understanding the epidemiology and occurrence in the reservoirs of mcr in E. coli on different continents of the world facilitates tracing how mcr genes are transmitted and determining the infection risks for humans. This knowledge can be used to reduce the incidence of zoonotic transmission by implementing the appropriate control programs.

Salmonellosis is one of the most important zoonoses in Europe and the world. Human infection may evolve in severe clinical diseases, with the need for hospitalization and antimicrobial treatment. Colistin is now considered an important antimicrobial to treat infections from multidrug- resistant Gram-negative bacteria, but the spreading of mobile colistin-resistance ( mcr ) genes has limited this option. We aimed to evaluate colistin minimum inhibitory concentration and the presence of mcr ( mcr-1 to mcr-9 ) genes in 236 Salmonella isolates previously collected from different animals and the environment between 2000 and 2020. Overall, 17.79% of isolates were resistant to colistin; no differences were observed in relation to years of isolation (2000-2005, 2009-2014, and 2015-2020), Salmonella enterica subspecies ( enterica , salamae , diarizonae , and houtenae ), origin of samples (domestic animals, wildlife, and environment), or animal category (birds, mammals, and reptiles); only recently isolated strains from houseflies showed the most resistance. Few isolates (5.93%) scored positive for mcr genes, in particular for mcr-1 , mcr-2 , mcr-4 , mcr-6 , and mcr-8 ; furthermore, only 2.54% of isolates were mcr -positive and colistin-resistant. Detected resistance to colistin was equally distributed among all examined Salmonella isolates and not always related to the presence of mcr genes.