Drug-resistant Neisseria gonorrhoeae poses an urgent threat to public health. Recently, sitafloxacin, a new-generation fluoroquinolone, has shown high in vitro activity against drug-resistant N. gonorrhoeae. However, data on its effectiveness in clinical isolates remains limited. In this study, we collected 507 N. gonorrhoeae isolates from 21 hospitals in Shanghai, China, during 2020 and 2021. Antimicrobial susceptibility testing revealed that sitafloxacin minimum inhibitory concentrations (MICs) exhibited a bimodal distribution, ranging from <0.004 to 2 mg/L. The MIC50 and MIC90 for sitafloxacin were 0.125 mg/L and 0.5 mg/L, respectively, which are 32 and 16 times lower than those for ciprofloxacin (4 mg/L and 8 mg/L, respectively). Sitafloxacin demonstrated high in vitro activity against isolates resistant to either ceftriaxone, azithromycin, or both. Notably, among the isolates with reduced sitafloxacin susceptibility (MIC ≥ MIC90), 83.7% (36/43) were identified as sequence type (ST) 8123. Further phylogenetic analysis showed that ST8123 has evolved into two subclades, designated as subclade-I and subclade-II. A majority of the isolates (80%, 36/45) within subclade-I exhibited reduced susceptibility to sitafloxacin. In contrast, all isolates from subclade-II were found to be susceptible to sitafloxacin. Subsequent genomic investigations revealed that the GyrA-S91F, D95Y, and ParC-S87N mutations, which were exclusively found in ST8123 subclade-I, might be linked to reduced sitafloxacin susceptibility. Our study reveals that sitafloxacin is a promising antibiotic for combating drug-resistant N. gonorrhoeae. However, caution is advised in the clinical application of sitafloxacin for treating N. gonorrhoeae infections due to the emergence of a clone exhibiting reduced susceptibility.

Background:The gut microbiota plays an important role in the development of neurological disorders such as Parkinson's disease and Alzheimer's disease. However, studies on the gut microbiota of patients with neurosyphilis (NS) were rarely reported. Methods:In this study, we collected fecal samples from 62 syphilis patients, including 39 with NS and 23 with non-NS. Among the NS patients, 18 were general paresis (GP). The white blood cell counts, protein concentrations, and Venereal Disease Research Laboratory test positive rates of cerebrospinal fluid from patients in NS or GP group were significantly higher than those from patients in non-NS group. 16S ribosomal RNA sequencing results revealed that the alpha and beta diversities of the gut microbiota were similar between NS and non-NS patients or GP and non-NS patients. Results:Linear discriminant analysis with effect size (LEfSe) analysis showed that some taxa, such as Coprobacter, were increased in both NS group and GP group, compared with non-NS group. Besides, the clade of Akkermansia was also overrepresented in GP Patients. Meanwhile, some taxa such as Clostridia_UCG-014 and SC-I-84 were underrepresented in NS patients. The abundances of class Bacilli and genus Alloprevotella were decreased in GP patients. Among them, the abundances of some taxa such as Coprobacter and Akkermansia have been reported to be associated with other neuropsychiatric disorders. Conclusion:Our findings suggest that the alternation of the gut microbiota in NS patients may contribute to the course of NS, which will deepen our understanding of NS.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) has disseminated globally and become a major threat to human life. The sequence type (ST) 11 CRKP is a dominant clone in Asia, especially China, but how this clone evolves in vivo , then adapts to host and facilitates dissemination remain largely unknown. We analyzed the genomic dynamics of 4 ST11-CRKP isolates sequencially isolated from the urine of a patient with initial fatal scrotal abscess and finally recovered without effective medication. Genomic differences were identified and their implications for pathogenesis and host adaptation were investigated. The related transcriptional pathways were further explored by RNA-Seq. Genomic analysis identified 4-24 mutations and 94%-100% were synonymous or intergenic. The mutation rate of ST11-CRKP was 2.1×10−6-1.7×10−5 substitutions/site/year over 47 days of antibiotics therapy. During this period, CRKP underwent several adaptive changes including tigecycline resistance and virulence attenuation. Tigecycline resistance was caused by ramR ribosomal binding site (RBS) deletion, which has been described by us previously. In this study, we demonstrated that mutations associated with acyltransferase ( act ) and ompK26 caused the virulence attenuation of ST11-CRKP . act deletion reduced the production of capsular polysaccharide and enhanced biofilm formation. RNA-Seq analysis revealed that act influenced the expression of ldhA , bglX , mtnK and metE which likely participate in capsular synthesis and biofilm formation. ompK26 affected the virulence by its overexpression caused by the deletion of upstream repressor binding site. Our finding suggested that the broad genomic diversity, high evolutionary capacity and rapid within-host adaptability of ST11-CRKP might contribute to the worldwide dissemination of this clone. IMPORTANCE Carbapenem-resistant Klebsiella pneumoniae (CRKP) has disseminated worldwide and can cause life threatening infections, including pneumonia, bloodstream infections, urinary tract infections, intra-abdominal infection, liver abscess and meningitis. CRKP infection is the leading cause of high mortality in clinical. The sequence type (ST) 11 CRKP is a dominant clone and accounts for 60% of CRKP infections in China. Recently, the ST11-CRKP with high transmissibility are increasingly identified. Understanding how this clone evolved is crucial in controlling its further dissemination. The significance of our research is identifying the in vivo genomic dynamics of ST11-CRKP and the genetic basis for ST11-CRKP to facilitate persistence and dissemination, which will has broader biomedical impacts on understanding of ST11-CRKP dissemination. Furthermore, our study also highlights the importance of monitoring the development of variation in antibiotics susceptibility and virulence of bacteria in clinical practice, considering that pathogens can rapidly adapt to host during the treatment.

淋病是由淋病奈瑟球菌(Neisseria gonorrhoeae)引起的化脓性炎性性传播疾病,可导致多种并发症及严重后遗症.抗菌药物是治疗淋病的主要手段.然而,世界范围内淋病奈瑟球菌对抗菌药物的耐药逐年严峻,甚至出现对一线治疗药物头孢曲松和阿奇霉素同时耐药的菌株.对淋病奈瑟球菌进行抗菌药物敏感性检测,并根据检测结果合理选用抗菌药物对淋病防治工作至关重要.本研究就常见的淋病奈瑟球菌抗菌药物敏感性检测方法进行综述,以期为相关疾病的临床诊治提供理论依据.