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 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 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 Characterization of a Multiresistant Mosaic Plasmid from a Fish Farm Sediment Exiguobacterium sp. Isolate Reveals Aggregation of Functional Clinic-Associated Antibiotic Resistance Genes

2013 ◽  
Vol 80 (4) ◽  
pp. 1482-1488 ◽  
Author(s):  
Jing Yang ◽  
Chao Wang ◽  
Jinyu Wu ◽  
Li Liu ◽  
Gang Zhang ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Antibiotic Resistance Genes ◽  
Mobile Elements ◽  
Fish Farms ◽  
Significant Similarity ◽  
Content Type ◽  
Genes Encoding ◽  
The Mean

ABSTRACTThe genusExiguobacteriumcan adapt readily to, and survive in, diverse environments. Our study demonstrated thatExiguobacteriumsp. strain S3-2, isolated from marine sediment, is resistant to five antibiotics. The plasmid pMC1 in this strain carries seven putative resistance genes. We functionally characterized these resistance genes inEscherichia coli, and genes encoding dihydrofolate reductase and macrolide phosphotransferase were considered novel resistance genes based on their low similarities to known resistance genes. The plasmid G+C content distribution was highly heterogeneous. Only the G+C content of one block, which shared significant similarity with a plasmid fromExiguobacterium arabatum, fit well with the mean G+C content of the host. The remainder of the plasmid was composed of mobile elements with a markedly lower G+C ratio than the host. Interestingly, five mobile elements located on pMC1 showed significant similarities to sequences found in pathogens. Our data provided an example of the link between resistance genes in strains from the environment and the clinic and revealed the aggregation of antibiotic resistance genes in bacteria isolated from fish farms.

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.

Multiplex PCR detection of the antibiotic resistance genes in Staphylococcus aureus strains isolated from auricular infections

2008 ◽  
Vol 53 (4) ◽  
pp. 357-362 ◽  
Author(s):  
T. Zmantar ◽  
K. Chaieb ◽  
F. Ben Abdallah ◽  
A. Ben Kahla-Nakbi ◽  
A. Ben Hassen ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antibiotic Resistance ◽  
Multiplex Pcr ◽  
Resistance Genes ◽  
Antibiotic Resistance Genes ◽  
Pcr Detection
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