Association of Antibacterial Susceptibility Profile with the Prevalence of Genes Encoding Efflux Proteins in the Bangladeshi Clinical Isolates of Staphylococcus aureus

Abstract

Expelling antibiotic molecules out of the cell wall through multiple efflux pumps is one of the potential mechanisms of developing resistance against a wide number of antibiotics in Staphylococcus aureus. The aim of this study was to investigate the association between the antibiotic susceptibility profile and the prevalence of different efflux pump genes i.e., norA, norB, norC, mepA, sepA, mdeA, qacA/B, and smr in the clinical isolates of S. aureus. Sixty clinical isolates were collected from a tertiary level hospital in Bangladesh. The disc diffusion method using ten antibiotics of different classes was used to discern the susceptibility profile. polymerase chain reaction (PCR) was employed to observe the resistance patterns and to detect the presence of plasmid and chromosomal encoded genes. Among the clinical isolates, 60% (36 out of 60) of the samples were Methicillin-resistant Staphylococcus aureus (MRSA), whereas 55% (33 out of 60) of the bacterial samples were found to be multi-drug resistant. The bacteria showed higher resistance to vancomycin (73.33%), followed by ciprofloxacin (60%), cefixime (53.33%), azithromycin (43.33%), and amoxicillin (31.67%). The prevalence of the chromosomally-encoded efflux genes norA (91.67%), norB (90%), norC (93.33%), mepA (93.33%), sepA (98.33%), and mdeA (93.33%) were extremely high with a minor portion of them carrying the plasmid-encoded genes qacA/B (20%) and smr (8.33%). Several genetic combinations of efflux pump genes were revealed, among which norA + norB + norC + mepA + sepA + mdeA was the most widely distributed combination among MRSA and MSSA bacteria that conferred resistance against ciprofloxacin and probably vancomycin. Based on the present study, it is evident that the presence of multiple efflux genes potentiated the drug extrusion activity and may play a pivotal role in the development of multidrug resistance in S. aureus.

Functional promiscuity of small multidrug resistance transporters from Staphylococcus aureus, Pseudomonas aeruginosa, and Francisella tularensis

“…Several studies have implicated SMR transporters in a variety of bacterial processes in addition to toxin efflux, including biofilm production (Andremont et al., 2010; Bay et al., 2017; Willsey et al., 2018), osmotic stress regulation (Bay & Turner, 2012), and toxic metabolite transport (Higashi et al., 2008; Higgins et al., 2019; Kermani et al., 2018). In addition, they are widespread in environmental and clinical isolates (Bjorland et al., 2001; Furi et al., 2013; Ignak et al., 2017; Katongole et al., 2020; Kiddee et al., 2013; Kondori & Mansury, 2023; McNeil et al., 2016, 2023; Suma et al., 2023; Zahedani et al., 2021), but our understanding of the functional role of the SMR transporters found in these isolates is limited. Recently, our lab discovered that the model SMR transporter from Escherichia coli , EmrE, confers susceptibility to some substrates rather than resistance.…”

Genomic alterations involved in fluoroquinolone resistance development in Staphylococcus aureus

“…Among chromosomal efflux proteins in S . aureus , NorA, NorB, and NorC which are encoded by norA , norB , and norC respectively, played an important role in decreased susceptibility to antibiotics especially FQs [ 36 – 38 ]. These proteins are belonged to the major facilitator superfamily (MFS) and negatively regulated by MgrA [ 37 ].…”