Biocide Selective TolC-Independent Efflux Pumps in Enterobacteriaceae

Abstract

Bacterial resistance to biocides used as antiseptics, dyes, and disinfectants is a growing concern in food preparation, agricultural, consumer manufacturing, and health care industries, particularly among Gram-negative Enterobacteriaceae, some of the most common community and healthcare-acquired bacterial pathogens. Biocide resistance is frequently associated with antimicrobial cross-resistance leading to reduced activity and efficacy of both antimicrobials and antiseptics. Multidrug resistant efflux pumps represent an important biocide resistance mechanism in Enterobacteriaceae. An assortment of structurally diverse efflux pumps frequently co-exist in these species and confer both unique and overlapping biocide and antimicrobial selectivity. TolC-dependent multicomponent systems that span both the plasma and outer membranes have been shown to confer clinically significant resistance to most antimicrobials including many biocides, however, a growing number of single component TolC-independent multidrug resistant efflux pumps are specifically associated with biocide resistance: small multidrug resistance (SMR), major facilitator superfamily (MFS), multidrug and toxin extruder (MATE), cation diffusion facilitator (CDF), and proteobacterial antimicrobial compound efflux (PACE) families. These efflux systems are a growing concern as they are rapidly spread between members of Enterobacteriaceae on conjugative plasmids and mobile genetic elements, emphasizing their importance to antimicrobial resistance. In this review, we will summarize the known biocide substrates of these efflux pumps, compare their structural relatedness, Enterobacteriaceae distribution, and significance. Knowledge gaps will be highlighted in an effort to unravel the role that these apparent “lone wolves” of the efflux-mediated resistome may offer.

Disinfectant and Antimicrobial Susceptibility Profiles of Campylobacter coli Isolated in 1998 to 1999 and 2015 from Swine and Commercial Pork Chops

“…The emergence of multidrug-resistant pathogens worldwide as well as a lack of new drug development is a concern in both human and veterinary medicine (CDC, 2013;Ventola, 2015). Research studies show that there is bacterial resistance to biocides (Davin-Regli & Pagès, 2012;Maillard, 2007;Russell, 2002;Slipski, Zhanel, & Bay, 2018;Tumah, 2009), and biocide use has resulted in cross-resistance to antimicrobials (Al-Jailawi, Ameen, & Al-Jeboori, 2013;Beier, Bischoff, Ziprin, Poole, & Nisbet, 2005;Braoudaki & Hilton, 2004;Davin-Regli & Pagès, 2012;Gnanadhas, Marathe, & Chakravortty, 2013;Maris, 1991;Romaro, Burgos, Pérez-Pulido, Gálvez, & Lucas, 2017;Sidhu, Heir, Leegaard, Wiger, & Holck, 2002;Wales & Davies, 2015;Wand, Bock, Bonney, & Sutton, 2017) producing a real risk that increased biocide use may exacerbate the trend of increasing AMR in pathogenic organisms (Fraise, 2002).…”

Whole Genome Sequencing Differentiates Presumptive Extended Spectrum Beta-Lactamase Producing Escherichia coli along Segments of the One Health Continuum

“…A number of qac subgroup members of small multidrug proteins have been previously identified in Enterobactericaeae including qacE, qacE∆1, qacF, qacG, and qacH. These genes are usually associated with plasmid-mediated class 1 integrons, which carry a variety of ARGs [70,71]. The qac genes are frequently found in combination with genes coding for β-lactams, aminoglycoside, sulfonamide, chloramphenicol, and trimethoprim resistance [4,72].…”

The β-Lactamase Gene Profile and a Plasmid-Carrying Multiple Heavy Metal Resistance Genes of Enterobacter cloacae

“…Recently, concerns have been raised regarding coselection for antibiotic resistance among bacteria exposed to disinfectants and heavy metals (particularly copper, zinc, and mercury) used in some livestock species as growth promoters and therapeutic agents [6]. Enterobacteriaceae (including E. coli , K. pneumoniae , and E. cloacae ) are highly adept at acquiring resistance genes to all disinfectants, heavy metals, and antibiotics through horizontal gene transfer between different bacteria within the environment; such genes include extended-spectrum beta-lactamases (ESBLs), copper and arsenic resistance systems (the pco and ars operons), and enzymes that hydrolyze cephalosporins (AmpC enzymes) [7, 8]. Many gram-negative organisms (such as E. coli , E. cloacae , and K. pneumoniae ) encode broad-substrate efflux pumps [6, 7, 9], and a variety of multidrug pumps that have activity against disinfectants are similarly encoded by some gram-positive organisms, including Staphylococcus aureus [9, 10].…”