Al-Asadi Sura Ali, Abdul Wahhab Batool Hazim, Bootwala Jamila, Alwatar Wifaq M Ali, Al-Kahachi Rusul Emaduldeen S
Department of Molecular and Medical Techniques, Biotechnology Research Centre, Al Nahrain University, Baghdad, Iraq.
Department of Microbiology, Faculty of Medicine, Mustansiriyah University, Baghdad, Iraq.
Microbiol Spectr. 2024 Oct 29;12(12):e0392623. doi: 10.1128/spectrum.03926-23.
The mortality rate of infectious diseases caused by is increasing. The enhanced antibiotic resistance among bacterial species through genetic transfer and mutations in the efflux mediating genes has made the treatment quite challenging. is an aerobic, gram-negative, and non-fermenting opportunistic pathogen found in immunocompromised patients. shows resistance against beta-lactams and other antibiotics through intrinsic resistance mechanisms, including multi-drug efflux pumps and beta-lactamases. In this study, the clinical isolate whole genome sequencing of data was analyzed to identify the genes and mutations responsible for antimicrobial resistance. The identified genes and their mutants were then subjected to structural analysis to better understand the impact of mutations on the protein structure, and domain analysis was performed to investigate the role of domains in antibiotic resistance. A total of 4 genes, and , were identified with significant mutations, whereas was shortlisted for further analysis based on the conserved regions, sequence alignment, and the maximum number of mutations. All the mutants of the gene contain the two common domains, the ABC transporter-like ATP-binding domain and the AAA + ATPase domain. These domains are crucial in efflux mediating drug transport and can be targeted to design novel drugs for treating infections caused by .IMPORTANCE species represent a significant threat as opportunistic pathogens, particularly in healthcare settings. Their resilience to antibiotics, demonstrated by strains like A. , poses a serious challenge in treating infections, especially in immunocompromised patients. This study emphasizes the critical need for heightened vigilance among healthcare professionals regarding infections. By analyzing the whole genome sequencing data of , the study sheds light on the genetic basis of antimicrobial resistance, aiding in more targeted treatment strategies. Furthermore, structural and domain analyses offer insights into how mutations impact protein structure and function, crucial for developing effective interventions. Ultimately, implementing rigorous sanitation measures and antibiotic stewardship protocols is needed to mitigate the spread of and safeguard vulnerable patient populations.
由[病原体名称]引起的传染病死亡率正在上升。细菌物种通过基因转移和外排介导基因的突变导致抗生素耐药性增强,这使得治疗颇具挑战性。[病原体名称]是一种需氧、革兰氏阴性、非发酵的机会性病原体,在免疫功能低下的患者中发现。[病原体名称]通过内在耐药机制,包括多药外排泵和β-内酰胺酶,对β-内酰胺类和其他抗生素表现出耐药性。在本研究中,对[病原体名称]临床分离株全基因组测序数据进行分析,以确定对抗菌药物耐药性负责的基因和突变。然后对鉴定出的基因及其突变体进行结构分析,以更好地了解突变对蛋白质结构的影响,并进行结构域分析以研究结构域在抗生素耐药性中的作用。总共鉴定出4个有显著突变的基因,即[基因名称1]、[基因名称2]、[基因名称3]和[基因名称4],而基于保守区域、序列比对和最大突变数,[基因名称4]被列入进一步分析名单。[基因名称4]的所有突变体都包含两个常见结构域,即ABC转运蛋白样ATP结合结构域和AAA + ATP酶结构域。这些结构域在介导药物外排运输中至关重要,可作为靶点来设计治疗由[病原体名称]引起的感染的新型药物。重要性[病原体名称]物种作为机会性病原体构成重大威胁,尤其是在医疗环境中。它们对抗生素的耐药性,如[菌株名称]菌株所表现的那样,在治疗感染方面构成严重挑战,特别是在免疫功能低下的患者中。本研究强调医疗专业人员对[病原体名称]感染提高警惕的迫切需要。通过分析[病原体名称]的全基因组测序数据,该研究揭示了抗菌药物耐药性的遗传基础,有助于制定更具针对性的治疗策略。此外,结构和结构域分析提供了关于突变如何影响蛋白质结构和功能的见解,这对于开发有效的干预措施至关重要。最终,需要实施严格的卫生措施和抗生素管理方案,以减轻[病原体名称]的传播并保护脆弱的患者群体。