Silent antibiotic resistance genes: A threat to antimicrobial therapy

Abstract

Purpose: Bacterial resistance to drugs is an increasing threat to the human community. In recent times the resistance of Gram negative bacteria to several classes of drug such as beta lactams, fluoroquinolones, aminoglycosides and colistin is gaining importance as it is involved in severe health complications in humans. In addition, many reports suggest the presence of silent antibiotic resistance genes with varying level of expression could also pose a severe threat to the public health.Methods & Materials: An E. coli isolate (MU2) phenotypically sensitive to quinolone/fluoroquinolone harboring qnrB resistance gene was selected in this study. To identify the silent nature of this resistance gene, plasmid sequencing was carried out. The growth kinetics of the isolate was determined and different stages were designated as Early Exponential Phase, Mid Exponential Phase (MEP), Late Exponential Phase, Early Stationary Phase and Late Stationary Phase. MU2 was subjected to various gut conditions such as bile shock, H 2 O 2 shock, anaerobic shock and NaCl shock at MEP. Further, TaqMan probe real time PCR was carried out to check the variations in the expression of qnrB in in vitro gut conditions.Results: We have earlier identified a plasmid-borne silent chloramphenicol resistance gene (catA1) in phenotypically sensitive Salmonella Weltevreden and the reason for its unexpressive nature was found to be the deletion of the promoter region. Further a fluoroquinolone sensitive E. coli isolated from UTI infection with a MIC of 0.047 mcg/ml for ciprofloxacin and 3 mcg/ml for nalidixic acid found to harbor a silent plasmid mediated quinolone resistance gene (qnrB). The promoter region and the gene itself was intact. The plasmid sequencing revealed the presence of prophage. Conclusion:The reversible nature of the silent antibiotic resistance gene can cause the emergence of fully antibiotic resistance revertants in the gut upon antibiotic challenge. Further, their presence in conjugative plasmid increases the risk of being transmitted to a susceptible strain and converting it to a resistant pathogen. However, in the present study, various in vitro gut shocks could not influence qnrB expression suggests that the mere presence of PMQR gene will not always confer fluoroquinolone resistance in bacterial pathogens.

Large-scale genomic analysis of antimicrobial resistance in the zoonotic pathogen Streptococcus suis

“…1). This same pattern is also common in other bacteria and up to 10% of S. aureus isolates [64][65][66][67][68]. These complexities have consequences for diagnostic investigation of AMR of S. suis using whole genome sequences.…”

Detection of antimicrobial resistance, pathogenicity, and virulence potentials of non-typhoidal Salmonella isolates at the Yaounde abattoir using whole genome sequencing technique

“…However, false negative cases were reported for each of the tested antibiotics. This mismatch between phenotypic and genotypic antimicrobial resistance was observed by previous authors who believed that some antimicrobial-resistant genes are "silent" in bacteria in vitro [9][10][11][12]. The "silent genes", are antibiotic resistance genes that were detected in the susceptible Salmonella isolates but failed to be expressed phenotypically.…”

“…However, the reasons why these genes were not expressed phenotypically are yet to be elucidated. Based on information reported by previous studies [9][10][11][12], the reason could be due the absence or impairment of the promoter sequence required for their expression. Another reason could be the presence of negative regulators of resistance genes that migt have downregulated their expression in vitro.…”

“…Another implication of the "silent genes" is that the host organisms may become an important reservoir of antibiotic-resistance to susceptible or major food pathogens beyond the Salmonella species via horizontal gene transfer or other mechanisms [10].This explains why several scientists considered "silent genes" as a significant potential threat to the therapeutic efficacy of antibiotics [10][11]. Remarkably, all the three Salmonella strains that exhibited phenotypic multidrug resistance were all Poona serovars and harbored the respective resistance genes (Tables 2 & 3).…”

“…All the genes involved in drug efflux are part of the resistance nodulation cell division (RND) efflux systems and only effectively perform their duty in synergy with TolC [11].…”