scholarly journals Deciphering pathogenicity and antibiotic resistance islands in methicillin-resistant Staphylococcus aureus genomes

Open Biology ◽  
2017 ◽  
Vol 7 (12) ◽  
pp. 170094 ◽  
Author(s):  
Mehul Jani ◽  
Soham Sengupta ◽  
Kelsey Hu ◽  
Rajeev K. Azad
Keyword(s):  
Staphylococcus Aureus ◽  
Drug Resistance ◽  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Antibiotic Resistance Genes ◽  
Genomic Islands ◽  
Hospital Environment ◽  
Gene Clustering ◽  
Methicillin Resistant ◽  
Modern Hospital

Staphylococcus aureus is a versatile pathogen that is capable of causing infections in both humans and animals. It can cause furuncles, septicaemia, pneumonia and endocarditis. Adaptation of S. aureus to the modern hospital environment has been facilitated, in part, by the horizontal acquisition of drug resistance genes, such as mecA gene that imparts resistance to methicillin. Horizontal acquisitions of islands of genes harbouring virulence and antibiotic resistance genes have made S. aureus resistant to commonly used antibiotics. To decipher genomic islands (GIs) in 22 hospital- and 9 community-associated methicillin-resistant S. aureus strains and classify a subset of GIs carrying virulence and resistance genes as pathogenicity and resistance islands respectively, we applied a host of methods for localizing genomic islands in prokaryotic genomes. Surprisingly, none of the frequently used GI prediction methods could perform well in delineating the resistance islands in the S. aureus genomes. Rather, a gene clustering procedure exploiting biases in codon usage for identifying horizontally transferred genes outperformed the current methods for GI detection, in particular in identifying the known islands in S. aureus including the SCC mec island that harbours the mecA resistance gene. The gene clustering approach also identified novel, as yet unreported islands, with many of these found to harbour virulence and/or resistance genes. These as yet unexplored islands may provide valuable information on the evolution of drug resistance in S. aureus .

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

2019 ◽  
Vol 17 (6) ◽  
pp. 930-943 ◽  
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.

scholarly journals Structural analysis of avibactam-mediated activation of the bla and mec divergons in methicillin-resistant Staphylococcus aureus

2020 ◽  
Vol 295 (32) ◽  
pp. 10870-10884 ◽  
Author(s):  
J. Andrew N. Alexander ◽  
Mariia Radaeva ◽  
Dustin T. King ◽  
Henry F. Chambers ◽  
Artem Cherkasov ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Physiological Role ◽  
Antibiotic Resistance Genes ◽  
Binding Pocket ◽  
Methicillin Resistant ◽  
Mortality And Morbidity ◽  
Expression Of Genes ◽  
Genes Encoding

Methicillin-resistant Staphylococcus aureus (MRSA) infections cause significant mortality and morbidity globally. MRSA resistance to β-lactam antibiotics is mediated by two divergons that control levels of a β-lactamase, PC1, and a penicillin-binding protein poorly acylated by β-lactam antibiotics, PBP2a. Expression of genes encoding these proteins is controlled by two integral membrane proteins, BlaR1 and MecR1, which both have an extracellular β-lactam–binding sensor domain. Here, we solved the X-ray crystallographic structures of the BlaR1 and MecR1 sensor domains in complex with avibactam, a diazabicyclooctane β-lactamase inhibitor at 1.6–2.0 Å resolution. Additionally, we show that S. aureus SF8300, a clinically relevant strain from the USA300 clone of MRSA, responds to avibactam by up-regulating the expression of the blaZ and pbp2a antibiotic-resistance genes, encoding PC1 and PBP2a, respectively. The BlaR1–avibactam structure of the carbamoyl-enzyme intermediate revealed that avibactam is bound to the active-site serine in two orientations ∼180° to each other. Although a physiological role of the observed alternative pose remains to be validated, our structural results hint at the presence of a secondary sulfate-binding pocket that could be exploited in the design of future inhibitors of BlaR1/MecR1 sensor domains or the structurally similar class D β-lactamases. The MecR1–avibactam structure adopted a singular avibactam orientation similar to one of the two states observed in the BlaR1–avibactam structure. Given avibactam up-regulates expression of blaZ and pbp2a antibiotic resistance genes, we suggest further consideration and research is needed to explore what effects administering β-lactam–avibactam combinations have on treating MRSA infections.

scholarly journals Molecular Characterization and Genotypic and Genotypic Evaluation of Antibiotic Resistance of Methicillin Resistant-staphylococcus Aureus Isolated From Raw Meat

2020 ◽  
Author(s):  
Roya Chabi
Keyword(s):  
Staphylococcus Aureus ◽  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Antibiotic Resistance Genes ◽  
Public Health Problem ◽  
Methicillin Resistant ◽  
Raw Meat ◽  
Significant Public Health ◽  
Mrsa Strains ◽  
Meat Samples

Abstract Methicillin-resistant Staphylococcus aureus (MRSA) is considered to be one of the most important causes of food-borne diseases. The present investigation was done to assess the phenotypic and genotypic characterization and distribution of Staphylococcal cassette chromosome mec types and Panton–Valentine leukocidin gene in the MRSA strains isolated from raw meat samples. Six-hundred and eighty meat samples were collected and cultured. MRSA strains were subjected to disk diffusion and Polymerase Chain Reaction. One-hundred and thirty-five out of 680 (18.38%) raw meat samples were positive for S. aureus. Seventy-nine out of 125 (63.20%) S. aureus strains were determined as MRSA. Raw sheep meat samples (75%) had the highest prevalence of MRSA, while raw camel had the lowest (50%). Fifty-eight out of 79 (73.41%) MRSA strains harbored the PVL gene. SCCmec IVa (39.65%), V (22.41%) and III (10.34%) were the most commonly detected types in the MRSA strains. MRSA strains harbored the highest prevalence of resistance against penicillin (100%), tetracycline (100%), gentamicin (65.51%) and erythromycin (56.89%). AadA1 (58.62%), tetK (56.89%), msrA (41.37%) and vatA (36.20%) were the most commonly detected antibiotic resistance genes. Simultaneous presence of PVL and antibiotic resistance genes in multi-drug resistant MRSA strains specifies significant public health problem.

scholarly journals Molecular characteristics and virulence gene profiles of Staphylococcus aureus isolates in Hainan, China

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Xuehan Li ◽  
Tao Huang ◽  
Kai Xu ◽  
Chenglin Li ◽  
Yirong Li
Keyword(s):  
Staphylococcus Aureus ◽  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Virulence Genes ◽  
Mainland China ◽  
Geographical Location ◽  
Antibiotic Resistance Genes ◽  
Virulence Gene ◽  
Molecular Characteristics ◽  
Staphylococcal Protein A

Abstract Background There have been no reports regarding the molecular characteristics, virulence features, and antibiotic resistance profiles of Staphylococcus aureus (S. aureus) from Hainan, the southernmost province of China. Methods Two hundred twenty-seven S. aureus isolates, consisting of 76 methicillin-resistant S. aureus (MRSA) and 151 methicillin-susceptible S. aureus (MSSA), were collected in 2013–2014 and 2018–2019 in Hainan, and investigated for their molecular characteristics, virulence genes, antibiotic resistance profiles and main antibiotic resistance genes. Results Forty sequence types (STs) including three new STs (ST5489, ST5492 and ST5493), and 79 Staphylococcal protein A (spa) types were identified based on multilocus sequence typing (MLST) and spa typing, respectively. ST398 (14.1%, 32/227) was found to be the most prevalent, and the prevalence of ST398-MSSA increased significantly from 2013 to 2014 (5.5%, 5/91) to 2018–2019 (18.4%, 25/136). Seventy-six MRSA isolates were subject to staphylococcus chromosomal cassette mec (SCCmec) typing. SCCmec-IVa was the predominant SCCmec type, and specifically, ST45-SCCmec IVa, an infrequent type in mainland China, was predominant in S. aureus from Hainan. The antibiotic resistance profiles and antibiotic resistance genes of S. aureus show distinctive features in Hainan. The resistant rates of the MRSA isolates to a variety of antibiotics were significantly higher than those of the MSSA isolates. The predominant erythromycin and tetracycline resistance genes were ermC (90.1%, 100/111) and tetK (91.8%, 78/85), respectively. Eleven virulence genes, including the Panton-Valentine leukocidin (pvl) and eta, were determined, and the frequency of eta and pvl were found to be 57.3 and 47.6%. Such high prevalence has never been seen in mainland China before. Conclusion S. aureus isolates in Hainan have unique molecular characteristics, virulence gene and antibiotic resistance profiles, and main antibiotic resistance genes which may be associated with the special geographical location of Hainan and local trends in antibiotic use.

scholarly journals Extreme genome selection towards complete antimicrobial resistance in a nosocomial strain of Stenotrophomonas maltophilia complex

2019 ◽  
Author(s):  
Sanjeet Kumar ◽  
Kanika Bansal ◽  
Prashant P. Patil ◽  
Amandeep Kaur ◽  
Satinder Kaur ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Antibiotic Resistance ◽  
Antimicrobial Resistance ◽  
Resistance Genes ◽  
Complete Genome Sequence ◽  
Complete Genome ◽  
Stenotrophomonas Maltophilia ◽  
Antibiotic Resistance Genes ◽  
Chromosomal Origin ◽  
Extreme Drug Resistance

ABSTRACTWe report first complete genome sequence and analysis of an extreme drug resistance (XDR) nosocomial Stenotrophomonas maltophilia that is resistant to the mainstream drugs i.e. trimethoprim/sulfamethoxazole (TMP/SXT) and levofloxacin. Taxonogenomic analysis revealed it to be a novel genomospecies of the Stenotrophomonas maltophilia complex (Smc). Comprehensive genomic investigation revealed fourteen dynamic regions (DRs) exclusive to SM866, consisting of diverse antibiotic resistance genes, efflux pumps, heavy metal resistance, various transcriptional regulators etc. Further, resistome analysis of Smc clearly depicted SM866 to be an enriched strain, having diversified resistome consisting of sul1 and sul2 genes. Interestingly, SM866 does not have any plasmid but it harbors two diverse super-integrons of chromosomal origin. Apart from genes for sulfonamide resistance (sul1 and sul2), both of these integrons harbor an array of antibiotic resistance genes linked to ISCR (IS91-like elements common regions) elements. These integrons also harbor genes encoding resistance to commonly used disinfectants like quaternary ammonium compounds and heavy metals like mercury. Hence, isolation of a novel strain belonging to a novel sequence type (ST) and genomospecies with diverse array of resistance from a tertiary care unit of India indicates extent and nature of selection pressure driving XDRs in hospital settings. There is an urgent need to employ complete genome based investigation using emerging technologies for tracking emergence of XDR at the global level and designing strategies of sanitization and antibiotic regime.Impact StatementThe hospital settings in India have one of the highest usage of antimicrobials and heavy patient load. Our finding of a novel clinical isolate of S. maltophilia complex with two super-integrons harbouring array of antibiotic resistance genes along with antimicrobials resistance genes indicates the extent and the nature of selection pressures in action. Further, the presence of ISCR type of transposable elements on both integrons not only indicates its propensity to transfer resistome but also their chromosomal origin suggests possibilities for further genomic/phenotypic complexities. Such complex cassettes and strain are potential threat to global health care. Hence, there is an urgent need to employ cost-effective long read technologies to keep vigilance on novel and extreme antimicrobial resistance pathogens in populous countries. There is also need for surveillance for usage of antimicrobials for hygiene and linked/rapid co-evolution of extreme drug resistance in nosocomial pathogens. Our finding of the chromosomal encoding XDR will shed a light on the need of hour to understand the evolution of an opportunistic nosocomial pathogen belonging to S. maltophilia.RepositoriesComplete genome sequence of Stenotrophomonas maltophilia SM866: CP031058

scholarly journals Molecular detection of antibiotic resistance genes in multidrug-resistant Staphylococcus aureus isolates from dog dental plaque

2019 ◽  
Vol 22 (4) ◽  
pp. 419-427
Author(s):  
S. Nouri Gharajalar ◽  
M. Onsori
Keyword(s):  
Staphylococcus Aureus ◽  
Antibiotic Resistance ◽  
Multiplex Pcr ◽  
Resistance Genes ◽  
Dental Plaque ◽  
Antibiotic Resistance Genes ◽  
Multidrug Resistant ◽  
Diffusion Method ◽  
Pcr Assay ◽  
Multiplex Pcr Assay

Multidrug resistant Staphylococcus aureus strains are a major health care problem both in humans and animals. In this work we described three multiplex PCR assays for detection of clinically relevant antibiotic resistance genes in S. aureus isolated from dog dental plaques. Thirty dental plaque samples were collected; then cultural, biochemical and molecular tests performed for isolation and identification of S. aureus from samples. The antibiotic susceptibility of the isolates were checked by Kirby Bauer disc diffusion method and the prevalence of antibiotic resistance genes determined using multiplex PCR assay. As a result S. aureus was isolated from 18 dog plaque samples. Fifteen of these isolates were resistant to penicillin. The mecA gene was more prevalent than blaZ among penicillin-resistant bacteria. Ten of the isolates were resistant to tetracycline. The percentage of tetM was higher than tetK among them. Also, 10 of the isolates were resistant to cefazolin among them bla TEM detected in higher rate than blaSHV and blaOXA-1. Hence multiplex PCR assay is a suitable method for detection of antibiotic resistance patterns of S. aureus isolates.

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