Emergence of methicillin resistance predates the clinical use of antibiotics

AbstractThe discovery of antibiotics more than 80 years ago has led to considerable improvements in human and animal health. Although antibiotic resistance in environmental bacteria is ancient, resistance in human pathogens is thought to be a modern phenomenon that is driven by the clinical use of antibiotics1. Here we show that particular lineages of methicillin-resistant Staphylococcus aureus—a notorious human pathogen—appeared in European hedgehogs in the pre-antibiotic era. Subsequently, these lineages spread within the local hedgehog populations and between hedgehogs and secondary hosts, including livestock and humans. We also demonstrate that the hedgehog dermatophyte Trichophyton erinacei produces two β-lactam antibiotics that provide a natural selective environment in which methicillin-resistant S. aureus isolates have an advantage over susceptible isolates. Together, these results suggest that methicillin resistance emerged in the pre-antibiotic era as a co-evolutionary adaptation of S. aureus to the colonization of dermatophyte-infected hedgehogs. The evolution of clinically relevant antibiotic-resistance genes in wild animals and the connectivity of natural, agricultural and human ecosystems demonstrate that the use of a One Health approach is critical for our understanding and management of antibiotic resistance, which is one of the biggest threats to global health, food security and development.

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Multi-drug resistance traits of methicillin-resistant Staphylococcus aureus and other Staphylococcal species from clinical and environmental sources

Journal of Water and Health ◽

10.2166/wh.2019.177 ◽

2019 ◽

Vol 17 (6) ◽

pp. 930-943 ◽

Cited By ~ 2

Author(s):

Adegboyega O. Oladipo ◽

Oluwatosin G. Oladipo ◽

Cornelius C. Bezuidenhout

Keyword(s):

Staphylococcus Aureus ◽

Drug Resistance ◽

Antibiotic Resistance ◽

Methicillin Resistant Staphylococcus Aureus ◽

Animal Health ◽

Antibiotic Resistance Genes ◽

Multi Drug Resistance ◽

Methicillin Resistant ◽

Hospital Effluent ◽

Resistance Traits

Abstract Multi-drug resistance traits of Staphylococcus species especially methicillin-resistant Staphylococcus aureus (MRSA) in the clinical settings are well established. Of environmental concern is hospital effluents discharging into wastewaters. This article investigated the prevalence and detection of antibiotic resistance genes in Staphylococcus species from clinical and environmental sources in Ile-Ife, Nigeria. Standard culture-based and molecular protocols were used. Seventy-six (27 clinical, 14 hospital effluent and 35 environmental) Staphylococcus isolates were recovered: 56.58% were coagulase-negative and 43.42% coagulase-positive (S. aureus). For the clinical isolates, 10, 6, 4, 4 and 1 were isolated from urine, skin, wounds, blood and pus, respectively. Isolates were resistant to methicillin and amoxycillin (91.7%), cloxacillin (88.0%), ciprofloxacin (84.0%), ofloxacin (83.3%), azithromycin (78.0%), ceftazidime (76.0%), gentamycin (75.0%), cefuroxime (75.0%) and erythromycin (72.0%). Nearly, all isolates (90.8%) had multiple antibiotic resistance (MAR) index >0.2. Overall MAR indices for Staphylococcus species isolated from the clinical, hospital effluent and environmental wastewaters were relatively similar (0.482; 0.500; 0.435). mecA, nuc and luk-pvl genes were detected in S. aureus, while mecA was detected in S. arlettae, S. sciuri, S. cohnii, S. epidermidis and S. saprophyticus. This study informs on the potential contamination of environmental waters downstream from hospitals and possible impacts that this could have on human and animal health.

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Quantification of antibiotic resistance genes and mobile genetic in dairy manure

PeerJ ◽

10.7717/peerj.12408 ◽

2021 ◽

Vol 9 ◽

pp. e12408

Author(s):

Yi Wang ◽

Pramod Pandey ◽

Colleen Chiu ◽

Richard Jeannotte ◽

Sundaram Kuppu ◽

...

Keyword(s):

Antibiotic Resistance ◽

Resistance Genes ◽

Management Practices ◽

Animal Health ◽

Dairy Farm ◽

Antibiotic Resistance Genes ◽

Dairy Farms ◽

Dairy Manure ◽

Manure Management ◽

Human Pathogens

Background Antibiotic resistance genes (ARGs) are considered to be emerging environmental contaminants of concern potentially posing risks to human and animal health, and this research studied the prevalence of antimicrobial resistance in dairy manure. Methods This study is focused on investigating prevalence of ARGs in California dairy farm manure under current common different manure management. A total of 33 manure samples were collected from multiple manure treatment conditions: (1) flushed manure (FM), (2) fresh pile (FP), (3) compost pile (CP), (4) primary lagoon (PL), and (5) secondary lagoon (SL). After DNA extraction, all fecal samples were screened by PCR for the presence of eight ARGs: four sulfonamide ARGs (sulI, sulII, sulIII, sulA), two tetracycline ARGs (tetW, tetO), two macrolide-lincosamide-streptogramin B (MLSB) ARGs (ermB, ermF). Samples were also screened for two mobile genetic elements (MGEs) (intI1, tnpA), which are responsible for dissemination of ARGs. Quantitative PCR was then used to screen all samples for five ARGs (sulII, tetW, ermF, tnpA and intI1). Results Prevalence of genes varied among sample types, but all genes were detectable in different manure types. Results showed that liquid-solid separation, piling, and lagoon conditions had limited effects on reducing ARGs and MGEs, and the effect was only found significant on tetW (p = 0.01). Besides, network analysis indicated that sulII was associated with tnpA (p < 0.05), and Psychrobacter and Pseudomonas as opportunistic human pathogens, were potential ARG/MGE hosts (p < 0.05). This research indicated current different manure management practices in California dairy farms has limited effects on reducing ARGs and MGEs. Improvement of different manure management in dairy farms is thus important to mitigate dissemination of ARGs into the environment.

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Cloning and Nucleotide Sequence Determination of the Entire mec DNA of Pre-Methicillin-Resistant Staphylococcus aureus N315

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.43.6.1449 ◽

1999 ◽

Vol 43 (6) ◽

pp. 1449-1458 ◽

Cited By ~ 271

Author(s):

T. Ito ◽

Y. Katayama ◽

K. Hiramatsu

Keyword(s):

Staphylococcus Aureus ◽

Antibiotic Resistance ◽

Methicillin Resistance ◽

Integration Site ◽

Bacterial Species ◽

Antibiotic Resistance Genes ◽

Direct Repeat ◽

Methicillin Resistant ◽

Reading Frame

ABSTRACT In methicillin-resistant Staphylococcus aureus, the methicillin resistance gene mecA is localized within a large chromosomal region which is absent in the methicillin-susceptibleS. aureus chromosome. The region, designatedmec DNA, is speculated to have originated from the genome of another bacterial species and become integrated into the chromosome of the S. aureus cell in the past. We report here cloning and determination of the structure of the entire mec DNA sequence from a Japanese S. aureus strain, N315. Themec DNA was found to be 51,669 bp long, including terminal inverted repeats of 27 bp and a characteristic pair of direct repeat sequences of 15 bp each: one is situated in the right extremity ofmec DNA, and the other is situated outside themec DNA and abuts the left boundary of mec DNA. The integration site of mec DNA was found to be located in an open reading frame (ORF) of unknown function, designatedorfX. Clusters of antibiotic resistance genes were noted inmec DNA carried by transposon Tn554 and an integrated copy of plasmid pUB110. Both the transposon and plasmid were integrated in the proximity of the mecA gene, the latter being flanked by a pair of insertion sequence IS431elements. Many ORFs other than those encoding antibiotic resistance were considered nonfunctional because of the acquired mutations or partial deletions found in the ORFs. Two ORFs potentially encoding novel site-specific recombinases were found in mec DNA. However, there was no ORF that might encode mecDNA-specific transposase or integrase proteins, indicating that themec DNA is not a transposon or a bacteriophage in nature.

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Investigation of the antibiotic resistance of staphylococcus species isolated from foods

Élelmiszervizsgálati Közlemények ◽

10.52091/evik-2021/2-1-eng ◽

2021 ◽

Vol 67 (2) ◽

pp. 3372-3382

Author(s):

Brigitta Horváth ◽

Ferenc Peles ◽

Judit Gasparikné Reichardt ◽

Edit Pocklán ◽

Rita Sipos ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Antibiotic Resistance ◽

Methicillin Resistance ◽

Multidrug Resistant ◽

Farm Animals ◽

The European Union ◽

Methicillin Resistant ◽

Maldi Tof Ms ◽

Maldi Tof ◽

Tof Ms

The presence of methicillin-resistant Staphylococcus aureus (MRSA) strains in the food chain has been confirmed by several studies in the European Union, but there are only limited data available in Hungary. The objective of the present study was to investigate the antibiotic resistance of Staphylococcus strains isolated from foods, using classical microbiological, molecular biological methods and the MALDI-TOF-MS technique, as well as the multi-locus sequence typing (MLST) of antibiotic resistant strains. During the study, 47 coagulase-positive (CPS) and 30 coagulase-negative (CNS) Staphylococcus isolates were collected. In the course of the MALDI-TOF-MS investigations, all CPS isolates (n=47) were found to be S. aureus species, while 8 different species were identified in the case of the CNS strains. Methicillin resistance was confirmed in two S. aureus strains, one of which had a sequence type not yet known, while the other MRSA strain was type ST398, which is the most common type of MRSA strain isolated from farm animals in the EU/EEA. (The abbreviation “MRSA” is often used in common parlance, but occasionally in the literature to denote “multidrug-resistant Staphylococcus aureus”. In the authors’ manuscript - the methicillin-resistant pathogen is correctly designated as such. Ed.)

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The resistome of common human pathogens

10.1101/140194 ◽

2017 ◽

Cited By ~ 4

Author(s):

Christian Munck ◽

Mostafa M. Hashim Ellabaan ◽

Michael Schantz Klausen ◽

Morten O.A. Sommer

Keyword(s):

Antibiotic Resistance ◽

Resistance Genes ◽

Bacterial Pathogens ◽

Antibiotic Resistance Genes ◽

Gene Clusters ◽

Species Level ◽

Natural Environments ◽

Human Pathogens ◽

Bacterial Genomes ◽

Risk Ranking

AbstractGenes capable of conferring resistance to clinically used antibiotics have been found in many different natural environments. However, a concise overview of the resistance genes found in common human bacterial pathogens is lacking, which complicates risk ranking of environmental reservoirs. Here, we present an analysis of potential antibiotic resistance genes in the 17 most common bacterial pathogens isolated from humans. We analyzed more than 20,000 bacterial genomes and defined a clinical resistome as the set of resistance genes found across these genomes. Using this database, we uncovered the co-occurrence frequencies of the resistance gene clusters within each species enabling identification of co-dissemination and co-selection patterns. The resistance genes identified in this study represent the subset of the environmental resistome that is clinically relevant and the dataset and approach provides a baseline for further investigations into the abundance of clinically relevant resistance genes across different environments. To facilitate an easy overview the data is presented at the species level at www.resistome.biosustain.dtu.dk.

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The Staphylococcal Cassette Chromosome mec (SCCmec) Analysis and Biofilm Formation of Methicillin-Resistant Staphylococcus cohnii Isolated from Clinical Samples in Tehran, Iran

Recent Patents on Anti-Infective Drug Discovery ◽

10.2174/1574891x16666210210101912 ◽

2021 ◽

Vol 16 ◽

Author(s):

Somaye Delfani ◽

Faranak Rezaei ◽

Setareh Soroush ◽

Pegah Shakib

Keyword(s):

Antibiotic Resistance ◽

Biofilm Formation ◽

Antibiotic Resistance Genes ◽

Mobile Element ◽

Diffusion Method ◽

Clinical Samples ◽

Coagulase Negative Staphylococci ◽

Methicillin Resistant ◽

Inducible Clindamycin Resistance ◽

Sccmec Types

Background: Methicillin-resistant coagulase-negative staphylococci is responsible for hospital and community-acquired infections. Objective: This study aimed to investigate the antibiotic-resistance patterns, antibiotic-resistance genes, namely, ermA, ermB, ermC, blaZ, msrA, tetK, tetM, mup, and vanA, biofilm formation, and prevalence of different SCCmec types among the Staphylococcus cohniistrains isolated from clinical samples in Tehran, Iran. Methods: In this study,S. cohniiisolates were screened from the clinical samples from March 2012 to February 2013 in Tehran, Iran.Antimicrobial susceptibility test and inducible clindamycin resistance were evaluated by disc diffusion method, andresistance genes were examined using Polymerase Chain Reaction (PCR) assays. Then, biofilm formation assay was analyzed by Microtiter-plate test to detect the icaA and icaDgenes. The SCCmec and the Arginine Catabolite Mobile Element (ACME) typing were performed using the PCRmethod. Results: FromtwentyS. cohnii, all isolates were resistant to cefoxitin. 95% of the S. cohnii was defined as multidrug resistance (MDR)strains. The ermB, ermC, and vanA genes were not detected in any isolates; however, the blaZ gene had the highest frequency.95% of the S. cohnii isolates produced biofilm. Also, 4 SCCmec types, including V, IV, III+ (C2), VIII+ (AB1), were identified. Therefore, the majority of SCCmec were untypable. Based on the ACME typing, arcA and opp3 genes were positive in 13 (65%) and 1 (5%) isolates, respectively. Conclusion: Due to the high antimicrobial resistance and the spread of untypableSCCmecamong the isolates studied, the control and treatment of methicillin-resistantS. cohnii in hospitals and public health centers is a significant concern.

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Studies on Bd0934 and Bd3507, Two Secreted Nucleases from Bdellovibrio bacteriovorus, Reveal Sequential Release of Nucleases during the Predatory Cycle

Journal of Bacteriology ◽

10.1128/jb.00150-20 ◽

2020 ◽

Vol 202 (18) ◽

Author(s):

Ewa Bukowska-Faniband ◽

Tilde Andersson ◽

Rolf Lood

Keyword(s):

Antibiotic Resistance ◽

Life Cycle ◽

Antibiotic Resistance Genes ◽

Human Pathogens ◽

Temporal Expression ◽

Bdellovibrio Bacteriovorus ◽

Exogenous Dna ◽

Content Type ◽

Genes Encoding ◽

Predatory Bacteria

ABSTRACT Bdellovibrio bacteriovorus is an obligate predatory bacterium that invades and kills a broad range of Gram-negative prey cells, including human pathogens. Its potential therapeutic application has been the subject of increased research interest in recent years. However, an improved understanding of the fundamental molecular aspects of the predatory life cycle is crucial for developing this bacterium as a “living antibiotic.” During intracellular growth, B. bacteriovorus secretes an arsenal of hydrolases, which digest the content of the host cell to provide growth nutrients for the predator, e.g., prey DNA is completely degraded by the nucleases. Here, we have, on a genetic and molecular level, characterized two secreted DNases from B. bacteriovorus, Bd0934 and Bd3507, and determined the temporal expression profile of other putative secreted nucleases. We conclude that Bd0934 and Bd3507 are likely a part of the predatosome but are not essential for the predation, host-independent growth, prey biofilm degradation, and self-biofilm formation. The detailed temporal expression analysis of genes encoding secreted nucleases revealed that these enzymes are produced in a sequential orchestrated manner. This work contributes to our understanding of the sequential breakdown of the prey nucleic acid by the nucleases secreted during the predatory life cycle of B. bacteriovorus. IMPORTANCE Antibiotic resistance is a major global concern with few available new means to combat it. From a therapeutic perspective, predatory bacteria constitute an interesting tool. They not only eliminate the pathogen but also reduce the overall pool of antibiotic resistance genes through secretion of nucleases and complete degradation of exogenous DNA. Molecular knowledge of how these secreted DNases act will give us further insight into how antibiotic resistance, and the spread thereof, can be limited through the action of predatory bacteria.

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Coexistence of Antibiotic Resistance Genes and Virulence Factors Deciphered by Large-Scale Complete Genome Analysis

mSystems ◽

10.1128/msystems.00821-19 ◽

2020 ◽

Vol 5 (3) ◽

Cited By ~ 3

Author(s):

Yu Pan ◽

Jiaxiong Zeng ◽

Liguan Li ◽

Jintao Yang ◽

Ziyun Tang ◽

...

Keyword(s):

Antibiotic Resistance ◽

Virulence Factors ◽

Resistance Genes ◽

Large Scale ◽

Antibiotic Resistance Genes ◽

Comprehensive Analysis ◽

Health Concern ◽

Human Pathogens ◽

Bacterial Genomes ◽

Gene Acquisition

ABSTRACT Widespread use of antibiotics has enhanced the evolution of highly resilient pathogens and poses a severe risk to human health via coselection of antibiotic resistance genes (ARGs) and virulence factors (VFs). In this study, we rigorously evaluate the abundance relationship and physical linkage between ARGs and VFs by performing a comprehensive analysis of 9,070 bacterial genomes isolated from multiple species and hosts. The coexistence of ARGs and VFs was observed in bacteria across distinct phyla, pathogenicities, and habitats, especially among human-associated pathogens. The coexistence patterns of gene elements in different habitats and pathogenicity groups were similar, presumably due to frequent gene transfer. A shorter intergenic distance between mobile genetic elements and ARGs/VFs was detected in human/animal-associated bacteria, indicating a higher transfer potential. Increased accumulation of exogenous ARGs/VFs in human pathogens highlights the importance of gene acquisition in the evolution of human commensal bacteria. Overall, the findings provide insights into the genic features of combinations of ARG-VF and expand our understanding of ARG-VF coexistence in bacteria. IMPORTANCE Antibiotic resistance has become a serious global health concern. Despite numerous case studies, a comprehensive analysis of ARG and VF coexistence in bacteria is lacking. In this study, we explore the coexistence profiles of ARGs and VFs in diverse categories of bacteria by using a high-resolution bioinformatics approach. We also provide compelling evidence of unique ARG-VF gene pairs coexisting in specific bacterial genomes and reveal the potential risk associated with the coexistence of ARGs and VFs in organisms in both clinical settings and environments.

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Characterization of antibiotic resistance genes in the species of the rumen microbiota

Nature Communications ◽

10.1038/s41467-019-13118-0 ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 9

Author(s):

Yasmin Neves Vieira Sabino ◽

Mateus Ferreira Santana ◽

Linda Boniface Oyama ◽

Fernanda Godoy Santos ◽

Ana Júlia Silva Moreira ◽

...

Keyword(s):

Antibiotic Resistance ◽

Resistance Genes ◽

Animal Health ◽

Antibiotic Resistance Genes ◽

Tetracycline Resistance ◽

Multidrug Resistant ◽

Resistant Bacteria ◽

Ruminal Bacteria ◽

Genes Encoding

AbstractInfections caused by multidrug resistant bacteria represent a therapeutic challenge both in clinical settings and in livestock production, but the prevalence of antibiotic resistance genes among the species of bacteria that colonize the gastrointestinal tract of ruminants is not well characterized. Here, we investigate the resistome of 435 ruminal microbial genomes in silico and confirm representative phenotypes in vitro. We find a high abundance of genes encoding tetracycline resistance and evidence that the tet(W) gene is under positive selective pressure. Our findings reveal that tet(W) is located in a novel integrative and conjugative element in several ruminal bacterial genomes. Analyses of rumen microbial metatranscriptomes confirm the expression of the most abundant antibiotic resistance genes. Our data provide insight into antibiotic resistange gene profiles of the main species of ruminal bacteria and reveal the potential role of mobile genetic elements in shaping the resistome of the rumen microbiome, with implications for human and animal health.

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