Wu Jiming, Zhang Jisheng, Wang Jianmin, Wang Jin, Liang Xushan, Wei Chunli, Long Wenzhang, Yang Yang, Chen Yuhui, Liao Mingjing, Liang Youtao, Yu Kaixin, Zhang Xiaoli
Department of Microbiology, Yongchuan Hospital of Chongqing Medical University, Chongqing, China.
Department of Pathogenic Biology, Basic Medicine of Jiamusi University, Jiamusi, China.
Front Microbiol. 2025 Mar 17;16:1553148. doi: 10.3389/fmicb.2025.1553148. eCollection 2025.
Due to the complexity of identifying the complex (ECC) at the species level, little is known about the distribution of carbapenem-resistant ECC (CRECC). Plasmid-mediated family genes are significant contributors to polymyxin resistance. The emergence of the gene has further complicated the landscape of polymyxin resistance in CRECC. Our study aimed to ascertain the prevalence of CRECC and the gene, and to elucidate the mechanisms underlying high-level resistance to polymyxin B (PB). In this study, we collected 212 non-replicating ECC strains, identifying 38 CRECC strains (17.9%, 38/212) and (71.1%, 27/38) as the predominant endemic strains. Among these, 10 CRECC strains (36.3%, 10/38) were found to harbor the gene. Interestingly, the presence of did not significantly impact PB resistance or impose a fitness cost. While overexpression of can enhance PB resistance within a certain range and may incur fitness costs, it does not result in high-level PB resistance. The PB resistance of 17 CRECC strains was notably increased (from 16 to 128 mg/L), accompanied by mutations in the / and genes. Notably, two novel insertion sequences, IS and IS, were discovered within the gene. The inactivation of results in the loss of its negative regulatory effect on the two-component system. Protein structure predictions indicated that mutations in primarily affect the phosphatase (HAMP) and histidine kinase domains. This research significantly expands our comprehension of the complexities of PB resistance, highlighting the multifactorial nature of antibiotic resistance mechanisms.
由于在物种水平上鉴定复杂肠杆菌科细菌（ECC）存在复杂性，关于耐碳青霉烯类ECC（CRECC）的分布情况知之甚少。质粒介导的家族基因是多粘菌素耐药性的重要促成因素。该基因的出现进一步使CRECC中多粘菌素耐药性的情况变得复杂。我们的研究旨在确定CRECC和该基因的流行情况，并阐明对多粘菌素B（PB）高水平耐药的潜在机制。在本研究中，我们收集了212株非重复性ECC菌株，鉴定出38株CRECC菌株（17.9%，38/212），其中[具体基因名称]（71.1%，27/38）为主要的地方流行菌株。其中，发现10株CRECC菌株（36.3%，10/38）携带该基因。有趣的是，[具体基因名称]的存在并未显著影响PB耐药性或带来适应性代价。虽然[具体基因名称]的过表达在一定范围内可增强PB耐药性且可能带来适应性代价，但不会导致高水平的PB耐药。17株CRECC菌株的PB耐药性显著增加（从16mg/L增至128mg/L），同时伴有[具体基因名称1]和[具体基因名称2]基因的突变。值得注意的是，在[具体基因名称]基因内发现了两个新的插入序列，即IS[具体编号1]和IS[具体编号2]。[具体基因名称]的失活导致其对双组分系统失去负调控作用。蛋白质结构预测表明，[具体基因名称]中的突变主要影响磷酸酶（HAMP）和组氨酸激酶结构域。本研究显著扩展了我们对PB耐药复杂性的理解，突出了抗生素耐药机制的多因素性质。
