Wang Liang-Chun, Litwin Madeline, Sahiholnasab Zahraossadat, Song Wenxia, Stein Daniel C
Department of Cell Biology and Molecular Genetics, University of Maryland College Park, College Park, MD 20904, USA.
Antibiotics (Basel). 2018 Jun 15;7(2):48. doi: 10.3390/antibiotics7020048.
Antibiotic resistance in (GC) has become an emerging threat worldwide and heightens the need for monitoring treatment failures. , a gram-negative bacterium responsible for gonorrhea, infects humans exclusively and can form aggregates during infection. While minimal inhibitory concentration (MIC) tests are often used for determining antibiotic resistance development and treatment, the knowledge of the true MIC in individual patients and how it relates to this laboratory measure is not known. We examined the effect of aggregation on GC antibiotic susceptibility and the relationship between bacterial aggregate size and their antibiotic susceptibility. Aggregated GC have a higher survival rate when treated with ceftriaxone than non-aggregated GC, with bacteria in the core of the aggregates surviving the treatment. GC lacking opacity-associated protein or pili, or expressing a truncated lipooligosaccharide, three surface molecules that mediate GC-GC interactions, reduce both aggregation and ceftriaxone survival. This study demonstrates that the aggregation of can reduce the susceptibility to antibiotics, and suggests that antibiotic utilization can select for GC surface molecules that promote aggregation which in turn drive pathogen evolution. Inhibiting aggregation may be a potential way of increasing the efficacy of ceftriaxone treatment, consequently reducing treatment failure.
淋球菌(GC)中的抗生素耐药性已成为全球范围内新出现的威胁,并增加了监测治疗失败情况的必要性。淋球菌是一种导致淋病的革兰氏阴性菌,仅感染人类,且在感染过程中会形成聚集体。虽然最小抑菌浓度(MIC)测试通常用于确定抗生素耐药性的发展和治疗情况,但个体患者中真实的MIC情况以及它与实验室测量值之间的关系尚不清楚。我们研究了聚集体对淋球菌抗生素敏感性的影响以及细菌聚集体大小与其抗生素敏感性之间的关系。用头孢曲松治疗时,聚集的淋球菌比未聚集的淋球菌具有更高的存活率,聚集体核心中的细菌在治疗后存活下来。缺乏opacity相关蛋白或菌毛,或表达截短的脂寡糖(这三种介导淋球菌 - 淋球菌相互作用的表面分子)的淋球菌,会减少聚集和头孢曲松治疗后的存活率。这项研究表明,淋球菌的聚集会降低对抗生素的敏感性,并表明抗生素的使用可能会选择促进聚集的淋球菌表面分子,进而推动病原体进化。抑制聚集可能是提高头孢曲松治疗效果、从而减少治疗失败的一种潜在方法。