Acinetobacter baumannii quorum-sensing signalling molecule induces the expression of drug-resistance genes

Abstract

Quorum-sensing signalling molecules such as N‑acyl homoserine lactones (AHLs) enable certain Gram‑negative bacteria to respond to environmental changes through behaviours, such as biofilm formation and flagellar movement. The present study aimed to identify Acinetobacter baumannii AHLs and assess their influence on antibiotic resistance. A clinical isolate of A. baumannii strain S (AbS) was collected from the wound of a burn patient and high‑performance liquid chromatography and tandem quadrupole or quadrupole time‑of‑flight high‑resolution mass spectrometry was used to identify AbS AHLs. Antibiotic sensitivity was assessed in an AHL‑deficient AbS mutant (AbS‑M), and the expression of drug-resistance genes in the presence of meropenem in AbS, AbS‑M and AbS‑M treated with the AHL N-3-hydroxy-dodecanoyl-homoserine lactone (N‑3‑OH‑C12‑HSL). AbS‑M was more sensitive to meropenem and piperacillin than wild‑type AbS, but resistance was restored by supplementation with N‑3‑OH‑C12‑HSL. In addition, meropenem‑treated AbS‑M expressed lower levels of the drug‑resistance genes oxacillinase 51, AmpC, AdeA and AdeB; treatment with N‑3‑OH‑C12‑HSL also restored the expression of these genes. Overall, the results of the present study indicate that N‑3‑OH‑C12‑HSL may be involved in regulating the expression of drug‑resistance genes in A. baumannii. Therefore, this quorum‑sensing signalling molecule may be an important target for treating multidrug‑resistant A. baumannii infections.

Figure 1.

Acinetobacter baumannii strain S growth curve and corresponding measurements of AHL activity. AHL, N-acyl homoserine lactone; OD, optical density.

Figure 2.

Ion chromatogram of the Acinetobacter baumannii strain S culture medium extract. A total of 30 precursor ions that could generate daughter ions at a mass-to-charge ratio of 102 were detected.

Figure 3.

MS profiles of N-3-OH-C₁₂-HSL. (A) MS2 spectrum of N-3-OH-C₁₂-HSL (m/z 300). (B) Secondary ion chromatogram of N-3-OH-C₁₂-HSL derived from Acinetobacter baumannii strain S obtained using high-performance liquid chromatography and tandem quadrupole MS (m/z 300≥m/z 102). MS, mass spectrometry; m/z, mass-to-charge ratio; N-3-OH-C₁₂-HSL, N-3-hydroxy-dodecanoyl-homoserine lactone.

Figure 4.

Major fragmentation pathway of N-3-hydroxy-dodecanoyl-homoserine lactone. m/z, mass-to-charge ratio.

Figure 5.

Activity of AHLs derived from AbS and AbS-M. The activity of AHLs derived from AbS-M (12.67±1.53) was significantly lower compared with AHLs derived from wild-type AbS (255.67±16.01) (P<0.01). AHL, N-acyl homoserine lactones; AbS, Acinetobacter baumannii strain S; AbS-M, AbS mutant.