Plasmids biocide resistance

Acquired, non-plasmid-encoded resistance to biocides can result when bacteria are exposed to gradually increasing concentrations of a biocide. Examples are provided by highly QAC-resistant Serratia marcescens, and chlorhexidine-resistant Ps. mirabilis, Ps. aeruginosa md Ser. marcescens. 

There is no evidence associating the presence or acquisition of plasmids with resistance to biocides in fungi, although acquired resistance (non-plas-mid) of yeasts to organic acids has been demonstrated [254]. 

Acquired microbial resistance has been extensively investigated with various antibiotics, but similar studies with biocides are fewer and more recent. It has been confirmed that many biocides can also be rendered meffective or less effective by acquired microbial resistance. This acquired resistance to both biocides and antibiotics may be genetic and/or biochemical [16, 26]. Chromosomal gene mutation and acquisition of plasmids and transposons by the microbes are the genetic modes that have been observed. As shown in Table I, plasmid-mediated biocide resistance can occur by... 

Table 4. Possible Mechanisms of Plasmid-mediated Biocide Resistance Adapted from [16].

Bacterial resistance to biocides (Table 13.2) is usually considered as being of two types (a) intrinsic (innate, natural), a natural property of an organism, or (b) acquired, either by chromosomal mutation or by the acquisition of plasmids or transposons. Intrinsic resistance to biocides is usually demonstrated by Gram-negative bacteria, mycobacteria and bacterial spores whereas acquired resistance can result by mutation or, more frequently, by the acquisition of genetic elements, e.g. plasmid- (or transposon-) mediated resistance to mercury compounds. Intrinsic resistance may also be exemplified by physiological (phenotypic) adaptation, a classical example of which is biofilm production. 

Mechanisms (1) Alteration of biocide (enzymatic inactivation) (2) Impaired uptake (3) Efflux Chromosomally mediated, but not usually relevant Applies to several biocides Not known Plasmid/Tn-mediated e.g. mercurials Less important Cationic biocides and antibiotic-resistant staphylococci... 

Acquired resistance to biocides results fiem genetie ehanges in a cell and arises either by mutation or by the acquisition of genetic material (plasmids, transposons) from another cell (Table 13.5). 

Intrinsic resistance to biocides as a consequence of bacterial degradative activities is thus not a major mechanism of insusceptibility. There are, of course, examples of plasmid-mediated enzymes that confer resistance to inorganic (and sometimes organic) mercurials and these will be discussed later... 

These mechanisms are of considerable microbiological and biochemical interest, although not all of the above agents find current use as biocides. The plasmid-mediated efflux pumps are particularly important, since efflux is one means whereby acquired resistance to antibiotics occurs (see earlier) and can be a mechanism of resistance to some clinically useful biocides (see later). No efflux pump comparable to those described for arsenate and cadmium [212] has yet been detected in silver-resistant bacteria [213] however, an up-to-date assessment of this subject is available [212]. 

Increased MICs of some biocides have been observed in S. aureus strains possessing a plasmid carrying genes encoding resistance to gentamicin (5) [214-220], Such biocides are chlorhexidine, QACs, acridines and diamidines together with ethidium bromide which is often studied in a similar manner. 

The ebr gene is identical to the qacC/qacD gene family [221], Sasatsu and his colleagues [230, 231] demonstrated that the nucleotide sequence of an amplified DNA fragment of the ebr gene from sensitive and resistant cells of S. aureus was identical and thus concluded that antiseptic-resistant cells result from an increase in copy number of a gene whose usual function is to remove toxic substances from normal sensitive cells of staphylococci (and also of enterococci). It is not always possible to demonstrate low-level resistance to cationic biocides in S. aureus [232-236] this could be due to the instability of plasmids in these clinical isolates. 

An association between antibiotic resistance and chlorhexidine and QAC resistance in Providencia stuartii and Proteus has been observed, but no evidence of a plasmid link obtained [25, 73, 287,288]. Chlorhexidine hypersensitivity has been noted in ciprofloxacin-resistant variants of Ps. aeruginosa [289] and vancomycin- and gentamicin-resistant strains of E. faecium retained sensitivity to the /usbiguanide [289, 290] and to other biocides [270-272], Anderson et al. [272] studied the inactivation kinetics of VRE and vancomycin-sensitive enterococci (VSE) exposed to environmental disinfectants at concentrations well below (extended dilutions) the recommended use-dilutions and found no differences in susceptibility of VRE and VSE. This type of approach is much more relevant than the widespread usage of MICs to measure responses to biocides. 

Plasmid R124 alters the cell surface of E. coli cells such that they show enhanced resistance to the QAC, cetrimide, and other agents [299]. Generally, plasmids do not promote resistance in Gram-negative bacteria to biocidal agents [300], although hospital isolates may be more resistant to biocides than laboratory strains [301]. It is to be wondered whether an Mdr system is associated with this resistance. 

Acquired resistance to biocides arises by the acquisition of extrachromoso-mal genetic elements (plasmids and transposons) or as a consequence of a chromosomal gene mutation [53, 236, 237]. Acquired resistance to chromosomal mutation can arise when bacteria are sequentially exposed to increasing concentrations of a biocide. 

Generally, however, there is minimal experimental evidence that plasmids are responsible for the development and spread of resistance to aldehydes, and, indeed, this is largely true for most biocides [53,237],... 

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