| Summary: | The consistently mutating bacterial genotypes appear to have accelerated the global challenge with antimicrobial resistance (AMR); it is therefore timely to investigate certain less-explored fields of targeting AMR mechanisms in bacterial pathogens. One of such areas is beta-lactamase (BLA) induction that can provide us with a collection of prospective therapeutic targets. The key genes (<i>ampD</i>, <i>ampE</i> and <i>ampG</i>) to which the AmpC induction mechanism is linked are also involved in regulating the production of fragmented muropeptides generated during cell-wall peptidoglycan recycling. Although the involvement of these genes in inducing class C BLAs is apparent, their effect on serine beta-lactamase (serine-BLA) induction is little known. Here, by using ∆<i>ampD</i> and ∆<i>ampE</i> mutants of <i>E. coli</i>, we attempted to elucidate the effects of <i>ampD</i> and <i>ampE</i> on the expression of serine-BLAs originating from <i>Enterobacteriaceae</i>, <i>viz</i>., CTX-M-15, TEM-1 and OXA-2. Results show that cefotaxime is the preferred inducer for CTX-M-15 and amoxicillin for TEM-1, whereas oxacillin for OXA-2. Surprisingly, exogenous BLA expressions are elevated in ∆<i>ampD</i> and ∆<i>ampE</i> mutants but do not always alter their beta-lactam susceptibility. Moreover, the beta-lactam resistance is increased upon <i>in trans</i> expression of <i>ampD</i>, whereas the same is decreased upon <i>ampE</i> expression, indicating a differential effect of <i>ampD</i> and <i>ampE</i> overexpression. In a nutshell, depending on the BLA, AmpD amidase moderately facilitates a varying level of serine-BLA expression whereas AmpE transporter acts likely as a negative regulator of serine-BLA.
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