Laboratory of Biotechnology, Chulabhorn Research Institute, Bangkok, Thailand.
Center of Excellence on Environmental Health and Toxicology (EHT), OPS, MHESI, Bangkok, Thailands.
PLoS One. 2024 Aug 28;19(8):e0309525. doi: 10.1371/journal.pone.0309525. eCollection 2024.
Stenotrophomonas maltophilia, a ubiquitous environmental bacterium, is an important cause of nosocomial infections. Although banned in some countries, paraquat (PQ) is commonly used to control weeds. In this study, we investigated the effects of increasing concentrations of PQ on S. maltophilia and its antimicrobial resistance. The sequential exposure of S. maltophilia K279a to increasing concentrations of PQ induces the formation of strains with increased resistance to PQ. Among the 400 PQ-resistant isolates tested, 70 clones were resistant to 16 μg/ml ciprofloxacin (CIP), and around 18% of the PQ/CIP-resistant isolates showed increased resistance to all the tested antimicrobials including, the aminoglycosides, quinolones, cephalosporin, chloramphenicol, and co-trimoxazole. The results of the expression analysis of the antimicrobial resistance genes in the five selected PQ/CIP-resistant isolates demonstrated the high expression of genes encoding efflux pumps (smeYZ, smaAB, smaCDEF, smeDEF, smeVWX, and smtcrA) and the enzymes aph(3')-IIc, blaL1, and blaL2. However, expression of the genes known for PQ resistance (i.e., mfsA and sod) were not altered relative to the wild-type levels. Whole genome sequence analysis identified gene mutations that could account for the antimicrobial resistance, namely, smeT (TetR family regulatory protein), rplA (ribosomal protein L1), and acnA (aconitase A). Ectopic expression of wild-type AcnA partially complemented the fluoroquinolone-resistant phenotype of the mutant with mutated acnA, which suggests the role of aconitase A in antimicrobial susceptibility. Exposure of S. maltophilia to PQ thus induces the development of strains that increase resistance to multiple antimicrobials.
嗜麦芽寡养单胞菌是一种普遍存在的环境细菌，是医院感染的重要原因。尽管百草枯（PQ）在一些国家被禁止使用，但它被广泛用于控制杂草。在这项研究中，我们研究了增加 PQ 浓度对嗜麦芽寡养单胞菌及其抗菌耐药性的影响。嗜麦芽寡养单胞菌 K279a 连续暴露于增加的 PQ 浓度会诱导形成对 PQ 耐药性增加的菌株。在测试的 400 个 PQ 耐药分离株中，有 70 个克隆对 16μg/ml 的环丙沙星（CIP）耐药，约 18%的 PQ/CIP 耐药分离株对所有测试的抗菌药物（包括氨基糖苷类、喹诺酮类、头孢菌素类、氯霉素和复方磺胺甲噁唑）的耐药性增加。对 5 个选定的 PQ/CIP 耐药分离株的抗菌药物耐药基因表达分析结果表明，编码外排泵（smeYZ、smaAB、smaCDEF、smeDEF、smeVWX 和 smtcrA）和酶 aph(3')-IIc、blaL1 和 blaL2 的基因高表达。然而，与野生型相比，PQ 耐药基因（即 mfsA 和 sod）的表达没有改变。全基因组序列分析确定了导致抗菌药物耐药的基因突变，即 smeT（TetR 家族调节蛋白）、rplA（核糖体蛋白 L1）和 acnA（ aconitase A）。野生型 AcnA 的异位表达部分补充了突变 acnA 导致的氟喹诺酮耐药表型，这表明 aconitase A 在抗菌药物敏感性中的作用。嗜麦芽寡养单胞菌暴露于 PQ 会诱导产生对多种抗菌药物耐药性增加的菌株。
