1 State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
2 Department of Infectious Diseases, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
J Dent Res. 2018 Sep;97(10):1092-1099. doi: 10.1177/0022034518782659. Epub 2018 Jun 21.
Growing evidence suggests the existence of new antibiotic resistance mechanisms. Recent studies have revealed that quorum-quenching enzymes, such as MacQ, are involved in both antibiotic resistance and cell-cell communication. Furthermore, some small bacterial regulatory RNAs, classified into RNA attenuators and small RNAs, modulate the expression of resistance genes. For example, small RNA sprX, can shape bacterial resistance to glycopeptide antibiotics via specific downregulation of protein SpoVG. Moreover, some bacterial lipocalins capture antibiotics in the extracellular space, contributing to severe multidrug resistance. But this defense mechanism may be influenced by Agr-regulated toxins and liposoluble vitamins. Outer membrane porin proteins and efflux pumps can influence intracellular concentrations of antibiotics. Alterations in target enzymes or antibiotics prevent binding to targets, which act to confer high levels of resistance in respiratory/oral bacteria. As described recently, horizontal gene transfer, including conjugation, transduction and transformation, is common in respiratory/oral microflora. Many conjugative transposons and plasmids discovered to date encode antibiotic resistance proteins and can be transferred from donor bacteria to transient recipient bacteria. New classes of mobile genetic elements are also being identified. For example, nucleic acids that circulate in the bloodstream (circulating nucleic acids) can integrate into the host cell genome by up-regulation of DNA damage and repair pathways. With multidrug resistant bacteria on the rise, new drugs have been developed to combate bacterial antibiotic resistance, such as innate defense regulators, reactive oxygen species and microbial volatile compounds. This review summaries various aspects and mechanisms of antibiotic resistance in the respiratory/oral microbiota. A better understanding of these mechanisms will facilitate minimization of the emergence of antibiotic resistance.
越来越多的证据表明存在新的抗生素耐药机制。最近的研究表明，群体感应淬灭酶（如 MacQ）参与抗生素耐药性和细胞间通讯。此外，一些小的细菌调节 RNA，分为 RNA 衰减子和小 RNA，调节耐药基因的表达。例如，小 RNA sprX 可以通过特异性下调蛋白 SpoVG 来影响细菌对糖肽类抗生素的耐药性。此外，一些细菌脂磷壁酸在外周空间捕获抗生素，导致严重的多药耐药性。但这种防御机制可能受到 Agr 调节毒素和脂溶性维生素的影响。外膜孔蛋白和外排泵可影响抗生素在细胞内的浓度。靶酶或抗生素的改变可防止与靶标结合，从而导致呼吸道/口腔细菌产生高水平的耐药性。如最近所述，水平基因转移，包括接合、转导和转化，在呼吸道/口腔微生物群中很常见。迄今为止发现的许多可移动转座子和质粒编码抗生素耐药蛋白，并可从供体细菌转移到短暂的受体细菌。新的移动遗传元件类也在被鉴定中。例如，在血液中循环的核酸（循环核酸）可以通过上调 DNA 损伤和修复途径整合到宿主细胞基因组中。随着多药耐药菌的增加，已经开发出一些新的药物来对抗细菌的抗生素耐药性，如先天防御调节剂、活性氧和微生物挥发性化合物。这篇综述总结了呼吸道/口腔微生物群中抗生素耐药性的各个方面和机制。更好地理解这些机制将有助于最大限度地减少抗生素耐药性的出现。
