Stable antibiotic resistance and rapid human adaptation in livestock-associated MRSA. - Related Documents




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460201.0000Stable antibiotic resistance and rapid human adaptation in livestock-associated MRSA. Mobile genetic elements (MGEs) are agents of horizontal gene transfer in bacteria, but can also be vertically inherited by daughter cells. Establishing the dynamics that led to contemporary patterns of MGEs in bacterial genomes is central to predicting the emergence and evolution of novel and resistant pathogens. Methicillin-resistant Staphylococcus aureus (MRSA) clonal-complex (CC) 398 is the dominant MRSA in European livestock and a growing cause of human infections. Previous studies have identified three categories of MGEs whose presence or absence distinguishes livestock-associated CC398 from a closely related and less antibiotic-resistant human-associated population. Here, we fully characterise the evolutionary dynamics of these MGEs using a collection of 1180 CC398 genomes, sampled from livestock and humans, over 27 years. We find that the emergence of livestock-associated CC398 coincided with the acquisition of a Tn916 transposon carrying a tetracycline resistance gene, which has been stably inherited for 57 years. This was followed by the acquisition of a type V SCCmec that carries methicillin, tetracycline, and heavy metal resistance genes, which has been maintained for 35 years, with occasional truncations and replacements with type IV SCCmec. In contrast, a class of prophages that carry a human immune evasion gene cluster and that are largely absent from livestock-associated CC398 have been repeatedly gained and lost in both human- and livestock-associated CC398. These contrasting dynamics mean that when livestock-associated MRSA is transmitted to humans, adaptation to the human host outpaces loss of antibiotic resistance. In addition, the stable inheritance of resistance-associated MGEs suggests that the impact of ongoing reductions in antibiotic and zinc oxide use in European farms on livestock-associated MRSA will be slow to be realised.202235762208
479910.9998Glycopeptide-resistant enterococci: a decade of experience. Since their first description in 1988, glycopeptide-resistant enterococci (GRE) have emerged as a significant cause of nosocomial infections and colonisations, particularly in Europe and the USA. Two major genetically distinct forms of acquired resistance, designated VanA and VanB, are recognised, although intrinsic resistance occurs in some enterococcal species (VanC) and a third form of acquired resistance (VanD) has been reported recently. The biochemical basis of each resistance mechanism is similar; the resistant enterococci produce modified peptidoglycan precursors that show decreased binding affinity for glycopeptide antibiotics. Although VanA resistance is detected readily in the clinical laboratory, the variable levels of vancomycin resistance associated with the other phenotypes makes detection less reliable. Under-reporting of VanB resistance as a result of a lower detection rate may account, in part, for the difference in the numbers of enterococci displaying VanA and VanB resistance referred to the PHLS Laboratory of Hospital Infection. Since 1987, GRE have been referred from >1100 patients in almost 100 hospitals, but 88% of these isolates displayed the VanA phenotype. It is possible that, in addition to the problems of detection, there may be a real difference in the prevalence of VanA and VanB resistance reflecting different epidemiologies. Our present understanding of the genetic and biochemical basis of these acquired forms of glycopeptide resistance has been gained mainly in the last 5 years. However, these relatively new enterococcal resistances appear still to be evolving; there have now been reports of transferable VanB resistance associated with either large chromosomally borne transposons or plasmids, genetic linkage of glycopeptide resistance and genes conferring high-level resistance to aminoglycoside antibiotics, epidemic strains of glycopeptide-resistant Enterococcus faecium isolated from multiple patients in numerous hospitals, and of glycopeptide dependence (mutant enterococci that actually require these agents for growth). The gene clusters responsible for VanA and VanB resistance are located on transposable elements, and both transposition and plasmid transfer have resulted in the dissemination of these resistance genes into diverse strains of several species of enterococci. Despite extensive research, knowledge of the origins of these resistances remains poor. There is little homology between the resistance genes and DNA from either intrinsically resistant gram-positive genera or from the soil bacteria that produce glycopeptides, which argues against direct transfer to enterococci from these sources. However, recent data suggest a more distant, evolutionary relationship with genes found in glycopeptide-producing bacteria. In Europe, VanA resistance occurs in enterococci isolated in the community, from sewage, animal faeces and raw meat. This reservoir suggests that VanA may not have evolved in hospitals, and its existence has been attributed, controversially, to use of the glycopeptide avoparcin as a growth promoter, especially in pigs and poultry. However, as avoparcin has never been licensed for use in the USA and, to date, VanB resistance has not been confirmed in non-human enterococci, it is clear that the epidemiology of acquired glycopeptide resistance in enterococci is complex, with many factors contributing to its evolution and global dissemination.19989788808
460120.9998CRISPR tracking reveals global spreading of antimicrobial resistance genes by Staphylococcus of canine origin. The close contact between pets and their owners is a potential source for microorganisms and genetic material exchange. Staphylococcus species considered as harmless inhabitants of animals' and humans' microbiota can act as reservoirs of antimicrobial resistance genes to more virulent species, thereby increasing their potential to resist drug therapy. This process could be inhibited by the antiplasmid immunity conferred by CRISPR systems. On the other hand, CRISPR spacer sequences can be explored as molecular clocks to track the history of genetic invasion suffered by a bacterial strain. To understand better the role of domestic dogs in human health as an antimicrobial resistance genes source, we analyzed 129 genomes of Staphylococcus strains of canine origin for the presence of CRISPR systems. Only 8% of the strains were positive for CRISPR, which is consistent with Staphylococcus role as gene reservoirs. The plasmidial origin or some spacers confirms the unsuccessful attempt of plasmid exchange in strains carrying CRISPRs. Some of these systems are within a staphylococcal cassette chromosome mec (SCCmec), sharing 98% of identity between their harboring strains. These CRISPRs' spacers reveal that this SCCmec was transferred between canine S. pseudintermedius strains, then to S. schleiferi and to Staphylococcus strains isolated from human beings. Our findings shows genetic evidence for the global spreading of pathogenic bacteria and the antimicrobial resistance genes carried by them and reinforce that, in the age of antimicrobial resistance, it is imperative that drug therapies consider the integrated nature of the relationship between pets and humans.201931030846
391430.9998Genomic Insights into Drug Resistance and Virulence Platforms, CRISPR-Cas Systems and Phylogeny of Commensal E. coli from Wildlife. Commensal bacteria act as important reservoirs of virulence and resistance genes. However, existing data are generally only focused on the analysis of human or human-related bacterial populations. There is a lack of genomic studies regarding commensal bacteria from hosts less exposed to antibiotics and other selective forces due to human activities, such as wildlife. In the present study, the genomes of thirty-eight E. coli strains from the gut of various wild animals were sequenced. The analysis of their accessory genome yielded a better understanding of the role of the mobilome on inter-bacterial dissemination of mosaic virulence and resistance plasmids. The study of the presence and composition of the CRISPR/Cas systems in E. coli from wild animals showed some viral and plasmid sequences among the spacers, as well as the relationship between CRISPR/Cas and E. coli phylogeny. Further, we constructed a single nucleotide polymorphisms-based core tree with E. coli strains from different sources (humans, livestock, food and extraintestinal environments). Bacteria from humans or highly human-influenced settings exhibit similar genetic patterns in CRISPR-Cas systems, plasmids or virulence/resistance genes-carrying modules. These observations, together with the absence of significant genetic changes in their core genome, suggest an ongoing flow of both mobile elements and E. coli lineages between human and natural ecosystems.202134063152
383440.9998What antimicrobial resistance has taught us about horizontal gene transfer. Horizontal gene transfer (HGT) has been responsible for the dissemination of numerous antimicrobial-resistance determinants throughout diverse bacterial species. The rapid and broad dissemination of resistance determinants by HGT, and subsequent selection for resistance imposed by the use of antimicrobials, threatens to undermine the usefulness of antimicrobials. However, vigilant surveillance of the emerging antimicrobial resistance in clinical settings and subsequent studies of resistant isolates create a powerful system for studying HGT and detecting rare events. Two of the most closely monitored phenotypes are resistance to beta-lactams and resistance to fluoroquinolones. Studies of resistance to these antimicrobials have revealed that (1) transformation occurs between different species of bacteria including some recipient species that were not previously known to be competent for natural transformation; (2) transduction may be playing an important role in generating novel methicillin-resistant Staphylococcus aureus (MRSA) strains, although the details of transferring the SCCmec element are not yet fully understood; (3) Resistance genes are probably moving to plasmids from chromosomes more rapidly than in the past; and (4) Resistance genes are aggregating upon plasmids. The linkage of numerous resistance genes on individual plasmids may underlie the persistence of resistance to specific antimicrobials even when use of those antimicrobials is discontinued. Further studies of HGT and methods for controlling HGT may be necessary to maintain the usefulness of antimicrobials.200919271198
404050.9998Molecular Insights into Antimicrobial Resistance Traits of Commensal Human Gut Microbiota. Antimicrobial resistance (AMR) among bacterial species that resides in complex ecosystems is a natural phenomenon. Indiscriminate use of antimicrobials in healthcare, livestock, and agriculture provides an evolutionary advantage to the resistant variants to dominate the ecosystem. Ascendency of resistant variants threatens the efficacy of most, if not all, of the antimicrobial drugs commonly used to prevent and/or cure microbial infections. Resistant phenotype is very common in enteric bacteria. The most common mechanisms of AMR are enzymatic modifications to the antimicrobials or their target molecules. In enteric bacteria, most of the resistance traits are acquired by horizontal gene transfer from closely or distantly related bacterial population. AMR traits are generally linked with mobile genetic elements (MGEs) and could rapidly disseminate to the bacterial species through horizontal gene transfer (HGT) from a pool of resistance genes. Although prevalence of AMR genes among pathogenic bacteria is widely studied in the interest of infectious disease management, the resistance profile and the genetic traits that encode resistance to the commensal microbiota residing in the gut of healthy humans are not well-studied. In the present study, we have characterized AMR phenotypes and genotypes of five dominant commensal enteric bacteria isolated from the gut of healthy Indians. Our study revealed that like pathogenic bacteria, enteric commensals are also multidrug-resistant. The genes encoding antibiotic resistance are physically linked with MGEs and could disseminate vertically to the progeny and laterally to the distantly related microbial species. Consequently, the AMR genes present in the chromosome of commensal gut bacteria could be a potential source of resistance functions for other enteric pathogens.201930009332
391560.9997Phylogenetic signature of lateral exchange of genes for antibiotic production and resistance among bacteria highlights a pattern of global transmission of pathogens between humans and livestock. The exchange of bacterial virulence factors driven by lateral gene transfer (LGT) can help indicate possible bacterial transmission among different hosts. Specifically, overlaying the phylogenetic signal of LGT among bacteria onto the distribution of respective isolation sources (hosts) can indicate patterns of transmission among these hosts. Here, we apply this approach towards a better understanding of patterns of bacterial transmission between humans and livestock. We utilize comparative genomics to trace patterns of LGT for an 11-gene operon responsible for the production of the antibiotic nisin and infer transmission of bacteria among respective host species. A total of 147 bacterial genomes obtained from NCBI were determined to contain the complete operon. Isolated from human, porcine and bovine hosts, these genomes represented six Streptococcus and one Staphylococcus species. Phylogenetic analyses of the operon sequences revealed a signature of frequent and recent lateral gene transfer that indicated extensive bacterial transmission between humans and pigs. For 11 isolates, we detected a Tn916-like transposon inserted into the operon. The transposon contained the tetM gene (tetracycline resistance) and additional phylogenetic analyses indicated transmission among human and animal hosts. The bacteria possessing the nisin operon and transposon were isolated from hosts distributed globally. These findings possibly reflect both the globalization of the food industry and an increasingly mobile and expanding human population. In addition to concerns regarding zoonosis, these findings also highlight the potential threat to livestock worldwide due to reverse zoonosis.201829631053
418070.9997Toward integrative genomics study of genetic resistance to Salmonella and Campylobacter intestinal colonization in fowl. Salmonella enterica serotypes Enteritidis and Typhimurium and Campylobacter jejuni are responsible for most cases of food poisoning in Europe. These bacteria do not cause severe disease symptoms in chicken, but they are easily propagated by symptomless chicken carriers which cannot be easily isolated. This animal tolerance is detrimental to food safety. In this particular case, increasing animal's resistance is not sufficient, since some animals considered as resistant are able to carry bacteria during several weeks without displaying disease symptoms. We review studies aimed at evaluating the resistance of chicken to Salmonella and Campylobacter intestinal colonization, either a few days or several weeks after infection. While studies of the genetic control of Campylobacter colonization are only beginning, mostly due to technical difficulties in infection protocols, genetic studies of Salmonella colonization have been conducted for now more than 20 years. They have initially reported an estimation of the genetic parameters associated with resistance to Salmonella colonization and are now aimed at identifying the genomic regions controlling variation of this trait in experimental lines and commercial populations. With the advent of high-throughput genomics, we are closer than ever to identify the true genes controlling resistance to Enterobacteria colonization in chicken. The comparison of genes involved in early resistance to intestinal colonization with genes controlling resistance to bacteria persistence several weeks after infection (i.e., carrier-state) should soon highlight the differences between the molecular mechanisms underlying those two distinct phenotypes. It will also be highly interesting to compare the genes or genomic regions controlling Campylobacter and Salmonella, in order to evaluate the feasibility of a selection conducted on both bacteria simultaneously.201223412643
442280.9997Diversity among multidrug-resistant enterococci. Enterococci are associated with both community- and hospital-acquired infections. Even though they do not cause severe systemic inflammatory responses, such as septic shock, enterococci present a therapeutic challenge because of their resistance to a vast array of antimicrobial drugs, including cell-wall active agents, all commercially available aminoglycosides, penicillin and ampicillin, and vancomycin. The combination of the latter two occurs disproportionately in strains resistant to many other antimicrobial drugs. The propensity of enterococci to acquire resistance may relate to their ability to participate in various forms of conjugation, which can result in the spread of genes as part of conjugative transposons, pheromone-responsive plasmids, or broad host-range plasmids. Enterococcal hardiness likely adds to resistance by facilitating survival in the environment (and thus enhancing potential spread from person to person) of a multidrug-resistant clone. The combination of these attributes within the genus Enterococcus suggests that these bacteria and their resistance to antimicrobial drugs will continue to pose a challenge.19989452397
432290.9997Multi-Drug Resistance in Bacterial Genomes-A Comprehensive Bioinformatic Analysis. Antimicrobial resistance is presently one of the greatest threats to public health. The excessive and indiscriminate use of antibiotics imposes a continuous selective pressure that triggers the emergence of multi-drug resistance. We performed a large-scale analysis of closed bacterial genomes to identify multi-drug resistance considering the ResFinder antimicrobial classes. We found that more than 95% of the genomes harbor genes associated with resistance to disinfectants, glycopeptides, macrolides, and tetracyclines. On average, each genome encodes resistance to more than nine different classes of antimicrobial drugs. We found higher-than-expected co-occurrences of resistance genes in both plasmids and chromosomes for several classes of antibiotic resistance, including classes categorized as critical according to the World Health Organization (WHO). As a result of antibiotic-resistant priority pathogens, higher-than-expected co-occurrences appear in plasmids, increasing the potential for resistance dissemination. For the first time, co-occurrences of antibiotic resistance have been investigated for priority pathogens as defined by the WHO. For critically important pathogens, co-occurrences appear in plasmids, not in chromosomes, suggesting that the resistances may be epidemic and probably recent. These results hint at the need for new approaches to treating infections caused by critically important bacteria.202337511196
4634100.9997Genome analysis reveals a biased distribution of virulence and antibiotic resistance genes in the genus Enterococcus and an abundance of safe species. Enterococci are lactic acid bacteria (LAB) that, as their name implies, often are found in the gastrointestinal tract of animals. Like many other gut-dwelling LAB, for example, various lactobacilli, they are frequently found in other niches as well, including plants and fermented foods from all over the world. In fermented foods, they contribute to flavor and other organoleptic properties, help extend shelf life, and some even possess probiotic properties. There are many positive attributes of enterococci; however, they have been overshadowed by the occurrence of antibiotic-resistant and virulent strains, often reported for the two species, Enterococcus faecalis and Enterococcus faecium. More than 40,000 whole-genome sequences covering 64 Enterococcus type species are currently available in the National Center for Biotechnology Information repository. Closer inspection of these sequences revealed that most represent the two gut-dwelling species E. faecalis and E. faecium. The remaining 62 species, many of which have been isolated from plants, are thus quite underrepresented. Of the latter species, we found that most carried no potential virulence and antibiotic resistance genes, an observation that is aligned with these species predominately occupying other niches. Thus, the culprits found in the Enterococcus genus mainly belong to E. faecalis, and a biased characterization has resulted in the opinion that enterococci do not belong in food. Since enterococci possess many industrially desirable traits and frequently are found in other niches besides the gut of animals, we suggest that their use as food fermentation microorganisms is reconsidered.IMPORTANCEWe have retrieved a large number of Enterococcus genome sequences from the National Center for Biotechnology Information repository and have scrutinized these for the presence of virulence and antibiotic resistance genes. Our results show that such genes are prevalently found in the two species Enterococcus faecalis and Enterococcus faecium. Most other species do not harbor any virulence and antibiotic resistance genes and display great potential for use as food fermentation microorganisms or as probiotics. The study contributes to the current debate on enterococci and goes against the mainstream perception of enterococci as potentially dangerous microorganisms that should not be associated with food and health.202540202320
9898110.9997Fitness Cost Evolution of Natural Plasmids of Staphylococcus aureus. Plasmids have largely contributed to the spread of antimicrobial resistance genes among Staphylococcus strains. Knowledge about the fitness cost that plasmids confer on clinical staphylococcal isolates and the coevolutionary dynamics that drive plasmid maintenance is still scarce. In this study, we aimed to analyze the initial fitness cost of plasmids in the bacterial pathogen Staphylococcus aureus and the plasmid-host adaptations that occur over time. For that, we first designed a CRISPR (clustered regularly interspaced palindromic repeats)-based tool that enables the removal of native S. aureus plasmids and then transferred three different plasmids isolated from clinical S. aureus strains to the same-background clinical cured strain. One of the plasmids, pUR2940, obtained from a livestock-associated methicillin-resistant S. aureus (LA-MRSA) ST398 strain, imposed a significant fitness cost on both its native and the new host. Experimental evolution in a nonselective medium resulted in a high rate pUR2940 loss and selected for clones with an alleviated fitness cost in which compensatory adaptation occurred via deletion of a 12.8-kb plasmid fragment, contained between two ISSau10 insertion sequences and harboring several antimicrobial resistance genes. Overall, our results describe the relevance of plasmid-borne insertion sequences in plasmid rearrangement and maintenance and suggest the potential benefits of reducing the use of antibiotics both in animal and clinical settings for the loss of clinical multidrug resistance plasmids.IMPORTANCE Plasmids are major agents in the spread of antibiotic resistance genes among bacteria. How plasmids and their hosts coevolve to reduce the fitness cost associated with plasmid carriage when bacteria grow in an antibiotic-free environment is not well understood. Here, we investigated the cost and the genetic adaptations that occur during evolution in the absence of antibiotics when the bacterial pathogen Staphylococcus aureus acquires a new plasmid. Our results show the occurrence, at the end of evolution, of plasmid rearrangements mediated by insertion sequences that lead to the loss of antimicrobial resistance genes from the plasmid and an alleviated fitness cost. Our results thus highlight the probable benefits of reducing the use of antibiotics in management programs for the selection of S. aureus clones carrying plasmids that no longer confer resistance.202133622733
3912120.9997Genomic Sequence Analysis of Methicillin- and Carbapenem-Resistant Bacteria Isolated from Raw Sewage. Antibiotic resistance is one of the largest threats facing global health. Wastewater treatment plants are well-known hot spots for interaction between diverse bacteria, genetic exchange, and antibiotic resistance. Nonpathogenic bacteria theoretically act as reservoirs of antibiotic resistance subsequently transferring antibiotic resistance genes to pathogens, indicating that evolutionary processes occur outside clinical settings and may drive patterns of drug-resistant infections. We isolated and sequenced 100 bacterial strains from five wastewater treatment plants to analyze regional dynamics of antibiotic resistance in the California Central Valley. The results demonstrate the presence of a wide diversity of pathogenic and nonpathogenic bacteria, with an arithmetic mean of 5.1 resistance genes per isolate. Forty-three percent of resistance genes were located on plasmids, suggesting that large levels of gene transfer between bacteria that otherwise may not co-occur are facilitated by wastewater treatment. One of the strains detected was a Bacillus carrying pX01 and pX02 anthrax-like plasmids and multiple drug resistance genes. A correlation between resistance genes and taxonomy indicates that taxon-specific evolutionary studies may be useful in determining and predicting patterns of antibiotic resistance. Conversely, a lack of geographic correlation may indicate that landscape genetic studies to understand the spread of antibiotic resistance genes should be carried out at broader scales. This large data set provides insights into how pathogenic and nonpathogenic bacteria interact in wastewater environments and the resistance genes which may be horizontally transferred between them. This can help in determining the mechanisms leading to the increasing prevalence of drug-resistant infections observed in clinical settings. IMPORTANCE The reasons for the increasing prevalence of antibiotic-resistant infections are complex and associated with myriad clinical and environmental processes. Wastewater treatment plants operate as nexuses of bacterial interaction and are known hot spots for genetic exchange between bacteria, including antibiotic resistance genes. We isolated and sequenced 100 drug-resistant bacteria from five wastewater treatment plants in California's Central Valley, characterizing widespread gene sharing between pathogens and nonpathogens. We identified a novel, multiresistant Bacillus carrying anthrax-like plasmids. This empirical study supports the likelihood of evolutionary and population processes in the broader environment affecting the prevalence of clinical drug-resistant infections and identifies several taxa that may operate as reservoirs and vectors of antibiotic resistance genes.202134132566
3936130.9997Impact of antibiotic use in the swine industry. Antibiotic resistance in bacteria associated with pigs not only affects pig production but also has an impact on human health through the transfer of resistant organisms and associated genes via the food chain. This can compromise treatment of human infections. In the past most attention was paid to glycopeptide and streptogramin resistance in enterococci, fluoroquinolone resistance in campylobacter and multi-drug resistance in Escherichia coli and salmonella. While these are still important the focus has shifted to ESBL producing organisms selected by the use of ceftiofur and cefquinome in pigs. In addition Livestock-associated methicillin-resistant Staphylococcus aureus (MRSA) suddenly emerged in 2007. We also need to consider multi-resistant strains of Streptococcus suis. Environmental contamination arising from piggery wastewater and spreading of manure slurry on pastures is also a growing problem.201424959754
3940140.9997Chicken Meat-Associated Enterococci: Influence of Agricultural Antibiotic Use and Connection to the Clinic. Industrial farms are unique, human-created ecosystems that provide the perfect setting for the development and dissemination of antibiotic resistance. Agricultural antibiotic use amplifies naturally occurring resistance mechanisms from soil ecologies, promoting their spread and sharing with other bacteria, including those poised to become endemic within hospital environments. To better understand the role of enterococci in the movement of antibiotic resistance from farm to table to clinic, we characterized over 300 isolates of Enterococcus cultured from raw chicken meat purchased at U.S. supermarkets by the Consumers Union in 2013. Enterococcus faecalis and Enterococcus faecium were the predominant species found, and antimicrobial susceptibility testing uncovered striking levels of resistance to medically important antibiotic classes, particularly from classes approved by the FDA for use in animal production. While nearly all isolates were resistant to at least one drug, bacteria from meat labeled as raised without antibiotics had fewer resistances, particularly for E. faecium Whole-genome sequencing of 92 isolates revealed that both commensal- and clinical-isolate-like enterococcal strains were associated with chicken meat, including isolates bearing important resistance-conferring elements and virulence factors. The ability of enterococci to persist in the food system positions them as vehicles to move resistance genes from the industrial farm ecosystem into more human-proximal ecologies.IMPORTANCE Bacteria that contaminate food can serve as a conduit for moving drug resistance genes from farm to table to clinic. Our results show that chicken meat-associated isolates of Enterococcus are often multidrug resistant, closely related to pathogenic lineages, and harbor worrisome virulence factors. These drug-resistant agricultural isolates could thus represent important stepping stones in the evolution of enterococci into drug-resistant human pathogens. Although significant efforts have been made over the past few years to reduce the agricultural use of antibiotics, continued assessment of agricultural practices, including the roles of processing plants, shared breeding flocks, and probiotics as sources for resistance spread, is needed in order to slow the evolution of antibiotic resistance. Because antibiotic resistance is a global problem, global policies are needed to address this threat. Additional measures must be taken to mitigate the development and spread of antibiotic resistance elements from farms to clinics throughout the world.201931471308
4800150.9997Human infections caused by glycopeptide-resistant Enterococcus spp: are they a zoonosis? Following the detection of glycopeptide-resistant enterococci (GRE) in 1986 and their subsequent global dissemination during the 1990s, many studies have attempted to identify the reservoirs and lines of resistance transmission as a basis for intervention. The eradication of reservoirs and the prevention of GRE spread is of major importance for two reasons: (i) the emergence of high-level glycopeptide resistance in invasive enterococcal clinical isolates that are already multiresistant, has left clinicians with therapeutic options that are only at the experimental stage; and (ii) the resistance genes may spread to more virulent bacterial species such as Staphylococcus aureus, Streptococcus pneumoniae and Clostridium difficile. VanA-type strains, resistant to high levels of both vancomycin and teicoplanin, are the most commonly encountered enterococci with acquired glycopeptide resistance in humans. A widespread VanA-type GRE reservoir was detected early in farm animals that were exposed to the glycopeptide growth-promoter avoparcin. Numerous studies have provided indirect evidence for the transfer of VanA-type GRE and their resistance determinants from animal reservoirs to humans. The data collected have expanded our understanding of the promiscuous nature of antibiotic resistance, and have provided the groundwork for logical decision-making with the objective of deterring the dissemination of resistant bacteria and of their resistance genes.200111688531
3897160.9997The use of aminoglycosides in animals within the EU: development of resistance in animals and possible impact on human and animal health: a review. Aminoglycosides (AGs) are important antibacterial agents for the treatment of various infections in humans and animals. Following extensive use of AGs in humans, food-producing animals and companion animals, acquired resistance among human and animal pathogens and commensal bacteria has emerged. Acquired resistance occurs through several mechanisms, but enzymatic inactivation of AGs is the most common one. Resistance genes are often located on mobile genetic elements, facilitating their spread between different bacterial species and between animals and humans. AG resistance has been found in many different bacterial species, including those with zoonotic potential such as Salmonella spp., Campylobacter spp. and livestock-associated MRSA. The highest risk is anticipated from transfer of resistant enterococci or coliforms (Escherichia coli) since infections with these pathogens in humans would potentially be treated with AGs. There is evidence that the use of AGs in human and veterinary medicine is associated with the increased prevalence of resistance. The same resistance genes have been found in isolates from humans and animals. Evaluation of risk factors indicates that the probability of transmission of AG resistance from animals to humans through transfer of zoonotic or commensal foodborne bacteria and/or their mobile genetic elements can be regarded as high, although there are no quantitative data on the actual contribution of animals to AG resistance in human pathogens. Responsible use of AGs is of great importance in order to safeguard their clinical efficacy for human and veterinary medicine.201931002332
4050170.9997Are Virulence and Antibiotic Resistance Genes Linked? A Comprehensive Analysis of Bacterial Chromosomes and Plasmids. Although pathogenic bacteria are the targets of antibiotics, these drugs also affect hundreds of commensal or mutualistic species. Moreover, the use of antibiotics is not only restricted to the treatment of infections but is also largely applied in agriculture and in prophylaxis. During this work, we tested the hypothesis that there is a correlation between the number and the genomic location of antibiotic resistance (AR) genes and virulence factor (VF) genes. We performed a comprehensive study of 16,632 reference bacterial genomes in which we identified and counted all orthologues of AR and VF genes in each of the locations: chromosomes, plasmids, or in both locations of the same genome. We found that, on a global scale, no correlation emerges. However, some categories of AR and VF genes co-occur preferentially, and in the mobilome, which supports the hypothesis that some bacterial pathogens are under selective pressure to be resistant to specific antibiotics, a fact that can jeopardize antimicrobial therapy for some human-threatening diseases.202235740113
4639180.9997Genomic and Phenotypic Characterization of Mastitis-Causing Staphylococci and Probiotic Lactic Acid Bacteria Isolated from Raw Sheep's Milk. Dairy products play a crucial role in human nutrition as they provide essential nutrients. However, the presence of diverse microorganisms in these products can pose challenges to food safety and quality. Here, we provide a comprehensive molecular characterization of a diverse collection of lactic acid bacteria (LAB) and staphylococci isolated from raw sheep's milk. Whole-genome sequencing, phenotypic characterization, and bioinformatics were employed to gain insight into the genetic composition and functional attributes of these bacteria. Bioinformatics analysis revealed the presence of various genetic elements. Important toxin-related genes in staphylococci that contribute to their pathogenic potential were identified and confirmed using phenotypic assays, while adherence-related genes, which are essential for attachment to host tissues, surfaces in the dairy environment, and the creation of biofilms, were also present. Interestingly, the Staphylococcus aureus isolates belonged to sequence type 5, which largely consists of methicillin-susceptible isolates that have been involved in severe nosocomial infections. Although genes encoding methicillin resistance were not identified, multiple resistance genes (RGs) conferring resistance to aminoglycosides, macrolides, and fluroquinolones were found. In contrast, LAB had few inherently present RGs and no virulence genes, suggesting their likely safe status as food additives in dairy products. LAB were also richer in bacteriocins and carbohydrate-active enzymes, indicating their potential to suppress pathogens and effectively utilize carbohydrate substrates, respectively. Additionally, mobile genetic elements, present in both LAB and staphylococci, may facilitate the acquisition and dissemination of genetic traits, including RGs, virulence genes, and metabolic factors, with implications for food quality and public health. The molecular and phenotypic characterization presented herein contributes to the effort to mitigate risks and infections (e.g., mastitis) and enhance the safety and quality of milk and products thereof.202337762186
4795190.9997Epidemiology and mechanisms of glycopeptide resistance in enterococci. PURPOSE OF REVIEW: This review updates epidemiologic trends and our understanding of glycopeptide resistance in enterococci. RECENT FINDINGS: Colonization and infection rates with vancomycin resistant enterococci continue to increase throughout the world while factors contributing to this rise continue to be defined. While no interventions exist to eradicate colonization, infection control procedures are cost effective and decrease the prevalence of vancomycin resistant enterococcal colonization and infection. New molecular methods show great promise in strengthening our ability to detect colonization with these bacteria. Furthermore, our understanding of the origin of vancomycin resistant enterococci continues to grow. Paenibacillus species found in soil have been found to carry homologues of vanA-associated glycopeptide resistance genes found in enterococci. Also, additional evidence supports previous data that VanB-associated resistance may have been horizontally transferred from gastrointestinal tract bacteria to enterococci. Finally, glycopeptide resistance has been transferred to methicillin-resistant Staphylococcus aureus in clinical practice on several occasions. SUMMARY: The prevalence of vancomycin resistant enterococci will likely continue to increase. Implementation of infection control strategies, in conjunction with deployment of advanced technologies for detection of vancomycin resistant enterococci, may curb this rise. The emergence of vancomycin resistant S. aureus is of concern.200516258324