Inactivation of MarR gene homologs increases susceptibility to antimicrobials in Bacteroides fragilis

Abstract

Bacteroides fragilis is the strict anaerobic bacteria most commonly found in human infections, and has a high mortality rate. Among other virulence factors, the remarkable ability to acquire resistance to a variety of antimicrobial agents and to tolerate nanomolar concentrations of oxygen explains in part their success in causing infection and colonizing the mucosa. Much attention has been given to genes related to multiple drug resistance derived from plasmids, integrons or transposon, but such genes are also detected in chromosomal systems, like the mar (multiple antibiotic resistance) locus, that confer resistance to a range of drugs. Regulators like MarR, that control expression of the locus mar, also regulate resistance to organic solvents, disinfectants and oxygen reactive species are important players in these events. Strains derived from the parental strain 638R, with mutations in the genes hereby known as marRI (BF638R_3159) and marRII (BF638R_3706) were constructed by gene disruption using a suicide plasmid. Phenotypic response of the mutant strains to hydrogen peroxide, cell survival assay against exposure to oxygen, biofilm formation, resistance to bile salts and resistance to antibiotics was evaluated. The results showed that the mutant strains exhibit statistically significant differences in their response to oxygen stress, but no changes were observed in survival when exposed to bile salts. Biofilm formation was not affected by either gene disruption. Both mutant strains however, became more sensitive to multiple antimicrobial drugs tested. This indicates that as observed in other bacterial species, MarR are an important resistance mechanism in B. fragilis.

Genomic Background and Phylogeny of cfiA-Positive Bacteroides fragilis Strains Resistant to Meropenem-EDTA

“…Exposure to several beta-lactams, carbapenems, fluoroquinolones, metronidazole, and certain chemical agents all induce the over-expression of efflux pump genes, thus promoting MDR in B. fragilis [ 23 ]. Other regulators of multiple antibiotic resistance such as the MarR family may be involved, as recently seen when the abolishment of the expression of MarR homologs increased susceptibility to several antimicrobials in B. fragilis [ 24 ]. The MarR sequences of the studied strains showed full identity, as they did with those of strains O21, BF8, and DCMSKEJBY0001B [ 4 ].…”

A sugar utilization phenotype contributes to the formation of genetic exchange communities in lactic acid bacteria

“…The multiple antibiotic resistance protein (MarR) family transcriptional regulator (Silva et al . 2018 ) is related to antibiotic resistance. Peptide methionine sulfoxide reductase (Walter et al .…”

Deletion of BmoR affects the expression of genes related to thiol/disulfide balance in Bacteroides fragilis

“…fragilis , besides BmoR, at least three other members of MarR have been annotated 22 . Two of them, MarRI and MarRII, have been associated with both oxidative stress and antimicrobial resistance 23 .…”