Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, 205 Duck Pond Drive, Blacksburg, VA 24061, United States.
Center for One Health Research, Virginia Polytechnic Institute and State University, 1410 Prices Fork Rd, Blacksburg, VA 24060, United States.
Pathog Dis. 2023 Jan 17;81. doi: 10.1093/femspd/ftad030.
The rapid occurrence of gonococcal resistance to all classes of antibiotics could lead to untreatable gonorrhea. Thus, development of novel anti-Neisseria gonorrhoeae drugs is urgently needed. Neisseria gonorrhoeae FA1090 is the most used in gonococcal infection mouse models because of its natural resistance to streptomycin. Streptomycin inhibits the urogenital commensal flora that permits gonococcal colonization. However, this strain is drug-susceptible and cannot be used to investigate the efficacy of novel agents against multidrug-resistant N. gonorrhoeae. Hence, to test the in vivo efficacy of new therapeutics against N. gonorrhoeae resistant to the frontline antibiotics, azithromycin, or ceftriaxone, we constructed streptomycin-resistant mutants of N. gonorrhoeae CDC-181 (azithromycin-resistant) and WHO-X (ceftriaxone-resistant). We identified the inoculum size needed to successfully colonize mice. Both mutants, CDC-181-rpsLA128G and WHO-X-rpsLA128G, colonized the genital tract of mice for 14 days with 100% colonization observed for at least 7 days. CDC-181-rpsLA128G demonstrated better colonization of the murine genital tract compared to WHO-X-rpsLA128G. Lower inoculum of WHO-X-rpsLA128G (105 and 106 CFU) colonized mice better than higher inoculum. Overall, our results indicate that CDC-181-rpsLA128G and WHO-X-rpsLA128G can colonize the lower genital tract of mice and are suitable to be used in mouse models to investigate the efficacy of antigonococcal agents.
淋球菌对所有类别的抗生素的快速耐药性可能导致无法治愈的淋病。因此，迫切需要开发新型抗淋病奈瑟菌药物。淋球菌 FA1090 是最常用于淋病感染小鼠模型的菌株，因为它对链霉素天然耐药。链霉素抑制了允许淋球菌定植的泌尿生殖道共生菌群。然而，该菌株对药物敏感，不能用于研究新型药物对多药耐药淋病奈瑟菌的疗效。因此，为了测试新疗法对耐一线抗生素（阿奇霉素或头孢曲松）的淋病奈瑟菌的体内疗效，我们构建了淋病奈瑟菌 CDC-181（阿奇霉素耐药）和 WHO-X（头孢曲松耐药）的链霉素耐药突变株。我们确定了成功定植小鼠所需的接种物大小。CDC-181-rpsLA128G 和 WHO-X-rpsLA128G 两种突变株都能在小鼠生殖道定植 14 天，至少有 7 天观察到 100%定植。CDC-181-rpsLA128G 比 WHO-X-rpsLA128G 更能定植小鼠生殖道。较低的 WHO-X-rpsLA128G 接种量（105 和 106 CFU）比高接种量更好地定植小鼠。总的来说，我们的结果表明，CDC-181-rpsLA128G 和 WHO-X-rpsLA128G 可以定植小鼠的下生殖道，适合用于小鼠模型来研究抗淋病奈瑟菌药物的疗效。
