Regulation of virulence and β-lactamase gene expression in Staphylococcus aureus isolates: cooperation of two-component systems in bloodstream superbugs

Abstract

Background Methicillin-resistant Staphylococcus aureus (MRSA)-bloodstream infections (BSI) are predominantly seen in the hospital or healthcare-associated host. Nevertheless, the interactions of virulence factor (VFs) regulators and β-lactam resistance in MRSA-BSI are unclear. This study aims to characterize the molecular relationship of two-component systems of VFs and the expression of the β-lactamase gene in MRSA-BSI isolates. In this study, 639 samples were collected from BSI and identified by phenotypic methods. We performed extensive molecular characterization, including SCCmec type, agr type, VFs gene profiles determinations, and MLST on isolates. Also, a quantitative real-time PCR (q-RT PCR) assay was developed for identifying the gene expressions. Results Ninety-one (91) S. aureus and 61 MRSA (67.0%) strains were detected in BSI samples. The presence of VFs and SCCmec genes in MRSA isolates were as follows: tst (31.4%), etA (18.0%), etB (8.19%), lukS-PVL (31.4%), lukF-PV (18.0%), lukE-lukD (16.3%), edin (3.2%), hla (16.3%), hlb (18.0%), hld (14.7%), hlg (22.9%), SCCmecI (16.3%), SCCmecII (22.9%), SCCmecIII (36.0%), SCCmecIV (21.3%), and SCCmecV (16.3%). Quantitative real-time PCR showed overexpression of mecRI and mecI in the toxigenic isolates. Moreover, RNAIII and sarA genes were the highest expressions of MRSA strains. The multi-locus sequence typing data confirmed a high prevalence of CC5, CC8, and CC30. However, ST30, ST22, and ST5 were the most prevalent in the resistant and toxigenic strains. Conclusion We demonstrated that although regulation of β-lactamase gene expressions is a significant contributor to resistance development, two-component systems also influence antibiotic resistance development in MRSA-BSI isolates. This indicates that resistant strains might have pathogenic potential. We also confirmed that some MLST types are more successful colonizers with a potential for MRSA-BSI.

Assessing the Potential of Gallic Acid and Methyl Gallate to Enhance the Efficacy of β-Lactam Antibiotics against Methicillin-Resistant Staphylococcus aureus by Targeting β-Lactamase: In Silico and In Vitro Studies

“…In the case of the tested antibiotics, ampicillin, amoxicillin, and penicillin G clearly demonstrated significantly reduced antibacterial efficacy against S. aureus ATCC 43300, indicating antibiotic resistance in this strain. S. aureus ATCC 43300 contains the β-lactamase gene expression, which is resistant to the β-lactam antibiotics by producing β-lactamase enzymes to hydrolyze the β-lactam ring [28]. Consequently, cloxacillin, a penicillinase-stable antibiotic, showed the highest antibacterial activity among the tested β-lactam antibiotics, whereas other penicillinase-unstable antibiotics demonstrated lower activities against MRSA ATCC 43300.…”

Prevalence and antimicrobial resistance profiling of Staphylococcus aureus isolated from traditional cheese in Yunnan, China

“…The rapid spread of MDR S. aureus harboring ARGs had become a major problem in veterinary and human medicine worldwide due to the difficulty of treating them. Most infections that lead to severe clinical implications for human health occur via pathogenic potential lineages and are classified as high-risk microbiological hazards in Hazard Analysis Critical Control Point (HACCP) (Ali et al 2021a;Dehbashi et al 2021;Fiaz et al 2021;Rodríguez-Lázaro et al 2017;Saima et al 2020). This present study is the first investigation to evaluate the spread of AMR and ARGs of S. aureus in Rubing and Rushan cheese in Yunnan province, China, through the integration of phenotypic approach and in silico genome-based methods using publicly available databases.…”

“…genetic element (MGE) embedded in a chromosome specified as staphylococcal cassette chromosomal mec (SCCmec), encoding for the production of a 78-kDa monofunctional transpeptidase penicillin-binding protein 2a (PBP2a) (Naorem et al 2020;Parvin et al 2021;Shahkarami et al 2014). The SCCmec cassette also plays an essential regulatory role in the pathogenicity of MRSA strains (Dehbashi et al 2021). Technological advances in high-throughput WGS and bioinformatics tools have developed a rapid and cost-effective framework for detecting and analyzing ARGs in isolated bacterial genomes and complex metagenomes obtained from food and environmental samples (Ali et al 2021b;Gupta et al 2020;Li et al 2021;Saima et al 2020).…”

Detection of blaOXA-145, blaOXA-224, blaOXA-539, and blaOXA-675 Genes and Carbapenem-Hydrolyzing Class D β-Lactamases (CHDLs) in Clinical Isolates of Pseudomonas aeruginosa Collected from West of Iran, Hamadan

“…Hydrophobic drugs enter bacterial cells through the phospholipid layer, while hydrophilic drugs enter through porins in Gram-negative bacteria (GNB) [ 1 , 2 ]. Some bacterial species, such as Pseudomonas aeruginosa , have an outer membrane that is less porous than other species, causing the bacteria to be less susceptible to antimicrobial agents [ 3 , 4 ].…”