Macrolides impact the growth ability of clinical <i>Pseudomonas aeruginosa</i> through quorum-sensing systems

The aim of the present study was to examine the impact of macrolides on the expression of virulence factors and QS-associated genes in clinical <i>P. aeruginosa</i> isolates. Among 60 clinical <i>P. aeruginosa</i>, pyocyanin production was detected in 27 (45%) isolates, which belonged to various STs. Erythromycin inhibited the production of pigments in 12 out of 27 isolates. Other antibiotic categories didn’t have an impact on production of pigments. Additionally, results showed that erythromycin sub-MIC inhibited the growth-rate in 17 isolates. Of note, in six isolates, the inhibition of growth-rate was greater when using both erythromycin and meropenem than using each antibiotic individually. Finally, addition of erythromycin down-regulated the expression of QS-associated genes (65.5%–81.3%) and almost all virulence-associated genes. In conclusion, our results confirmed that macrolides could be used in combination with last-line antibiotics, such as carbapenems, to treat infections caused by multidrug-resistant Gram-negative bacteria.本研究旨在考察大环内酯类抗生素对临床铜绿假单胞菌（Pseudomonas aeruginosa, P. aeruginosa）分离株中毒力因子及群体感应（Quorum Sensing, QS）相关基因表达的影响。在60株临床铜绿假单胞菌分离株中，27株（占比45%）可检测到绿脓菌素产生，这些菌株分属于不同的序列型（Sequence Type, ST）。红霉素可抑制27株菌株中的12株的色素生成，其余类别抗生素对该类色素的产生无影响。此外，研究结果显示，红霉素亚抑菌浓度（sub-minimum inhibitory concentration, sub-MIC）可抑制17株菌株的生长速率。值得注意的是，在6株菌株中，联合使用红霉素与美罗培南时，对生长速率的抑制效果强于单独使用任一抗生素。最后，添加红霉素可下调群体感应相关基因的表达，下调幅度达65.5%~81.3%，且几乎所有毒力相关基因的表达均被下调。综上，本研究结果证实，大环内酯类抗生素可与碳青霉烯类等最后一线抗生素联合使用，用于治疗多重耐药革兰阴性菌引发的感染。