Tan Bernice Siu Yan, Mohan Lalit, Watthanaworawit Wanitda, Ngamprasertchai Thundon, Nosten Francois H, Ling Clare, Bifani Pablo
A*STAR Infectious Diseases Labs (A*IDL), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
Infectious Diseases Translational Research Programme, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Front Microbiol. 2024 May 3;15:1368813. doi: 10.3389/fmicb.2024.1368813. eCollection 2024.
Florfenicol (Ff) is an antimicrobial agent belonging to the class amphenicol used for the treatment of bacterial infections in livestock, poultry, and aquaculture (animal farming). It inhibits protein synthesis. Ff is an analog of chloramphenicol, an amphenicol compound on the WHO essential medicine list that is used for the treatment of human infections. Due to the extensive usage of Ff in animal farming, zoonotic pathogens have developed resistance to this antimicrobial agent. There are numerous reports of resistance genes from organisms infecting or colonizing animals found in human pathogens, suggesting a possible exchange of genetic materials. One of these genes is , a gene that encodes for an efflux pump that removes Ff from bacterial cells, conferring resistance against amphenicol, and is often associated with mobile genetic elements and other resistant determinants. In this study, we analyzed bacterial isolates recovered in rural Thailand from patients and environmental samples collected for disease monitoring. Whole genome sequencing was carried out for all the samples collected. Speciation and genome annotation was performed revealing the presence of the gene in the bacterial genome. The minimum inhibitory concentration (MIC) was determined for Ff and chloramphenicol. Chromosomal and phylogenetic analyses were performed to investigate the acquisition pattern of the gene. The presence of a conserved gene in unrelated . isolated from human bacterial infections and environmental samples was observed, suggesting multiple and independent inter-species genetic exchange of drug-resistant determinants. The was found to be in the variable region containing various mobile genetic elements and other antibiotic resistance determinants; however, no evidence of HGT could be found. The gene identified in this study is chromosomal for all isolates. The study highlights a plausible impact of antimicrobials used in veterinary settings on human health. Ff shares cross-resistance with chloramphenicol, which is still in use in several countries. Furthermore, by selecting for -resistance genes, we may be selecting for and facilitating the zoonotic and reverse zoonotic exchange of other flanking resistance markers between human and animal pathogens or commensals with detrimental public health consequences.
氟苯尼考（Ff）是一种属于甲砜霉素类的抗菌剂，用于治疗家畜、家禽和水产养殖（动物养殖）中的细菌感染。它抑制蛋白质合成。Ff是氯霉素的类似物，氯霉素是世界卫生组织基本药物清单上的一种甲砜霉素化合物，用于治疗人类感染。由于Ff在动物养殖中的广泛使用，人畜共患病原体已对这种抗菌剂产生耐药性。有许多报告称，在人类病原体中发现了来自感染或定植动物的生物体的耐药基因，这表明可能存在遗传物质的交换。其中一个基因是 ，该基因编码一种外排泵，可将Ff从细菌细胞中清除，赋予对甲砜霉素的抗性，并且通常与移动遗传元件和其他抗性决定因素相关。在本研究中，我们分析了从泰国农村患者以及为疾病监测而采集的环境样本中分离出的细菌。对所有采集的样本进行了全基因组测序。进行了物种鉴定和基因组注释，揭示了细菌基因组中 基因的存在。测定了Ff和氯霉素的最低抑菌浓度（MIC）。进行了染色体和系统发育分析，以研究 基因的获得模式。在从人类细菌感染和环境样本中分离出的不相关的 中观察到保守的 基因的存在，这表明耐药决定因素存在多次独立的种间遗传交换。发现 位于包含各种移动遗传元件和其他抗生素抗性决定因素的可变区域；然而，未发现水平基因转移的证据。本研究中鉴定的 基因在所有分离株中均为染色体基因。该研究强调了兽医环境中使用的抗菌剂对人类健康可能产生的影响。Ff与氯霉素存在交叉耐药性，氯霉素在几个国家仍在使用。此外，通过选择 -耐药基因，我们可能正在选择并促进人类和动物病原体或共生菌之间其他侧翼抗性标记的人畜共患病和反向人畜共患病交换，从而对公共卫生产生有害影响。
