Biology subjects

Su, X.-H.

Publications and source records attributed to Su, X.-H..

5 recordsLinked to original sources

bioRxiv2022

In vitro activity of ertapenem against Neisseria gonorrhoeae clinical isolates with decreased susceptibility or resistance to extended spectrum cephalosporins in Nanjing, China (2013-2019)

ObjectiveNeisseria gonorrhoeae isolates collected in Nanjing, China, that possessed decreased susceptibility (or resistance) to extended spectrum cephalosporins (ESCs), were examined for susceptibility to ertapenem and their sequence types determined. MethodsCeftriaxone and cefixime minimum inhibitory concentrations (MICs) [≥] 0.125 mg/L and [≥] 0.25 mg/L, respectively, were first determined in 259 strains isolated between 2013 and 2019 and then MICs of ertapenem were measured using the antimicrobial gradient epsilometer test (Etest). Genetic determinants of ESC resistance and multi-antigen sequence typing (NG-MAST) were also determined to analyze associations with ertapenem susceptibility. ResultsAll isolates displayed ertapenem MICs between 0.006 mg/L-0.38 mg/L; the overall MIC50 and MIC90 were 0.032 mg/L and 0.125 mg/L. 44 (17.0%) isolates displayed ertapenem MICs of [≥] 0.125 mg/L; 10 (3.9%) had MICs [≥] 0.25 mg/L. The proportion of isolates with ertapenem MICs [≥] 0.125 mg/L increased from 4.0% in 2013, to 20.0% in 2019 ({chi}2= 24.144, P<0.001; Chi square test for linear trend). The penA mosaic allele was present in a significantly higher proportion of isolates with ertapenem MICs [≥] 0.125 mg/L compared to isolates with MICs [≤] 0.094 mg/L) (97.7% vs. 34.9%, respectively; {chi}2=58.158, P<0.001). ST5308 was the most prevalent NG-MAST type (8.5%); ST5308 was also significantly more common among isolates with ertapenem MICs [≥] 0.125 mg/L vs. isolates with MICs [≤] 0.094mg/L (22.7% and 5.6% respectively; {chi}2=13.815, P=0.001). ConclusionsErtapenem may be effective therapy for gonococcal isolates with decreased susceptibility or resistance to ESCs and isolates with identifiable genetic resistance determinants.

microbiology↗

bioRxiv2021

In vitro efficacy of gentamicin against multidrug-resistant Neisseria gonorrhoeae: synergy of three gentamicin antimicrobial combinations

ObjectivesTo determine in vitro activities of gentamicin alone and in combination with ceftriaxone, ertapenem and azithromycin against multidrug-resistant (MDR) N. gonorrhoeae isolates. Methods407 isolates from Nanjing, China, obtained in 2016 and 2017, had minimum inhibitory concentrations (MICs) determined for gentamicin using the agar dilution method. Antimicrobial combinations were also tested in 97 MDR strains using the antimicrobial gradient epsilometer test (Etest); results ranging from synergy to antagonism were interpreted using the fractional inhibitory concentration (FICI). ResultsAll 407 gonococcal isolates were susceptible to gentamicin. MICs ranged from 2 mg/L to 16 mg/L. Synergy was demonstrated in 16.5%(16/97), 27.8%(27/97) and 8.2%(8/97) MDR strains when gentamicin was combined with ceftriaxone [geometric mean (GM) FICI; 0.747], ertapenem (GM FICI; 0.662) and azithromycin (GM FICI; 1.021), respectively. No antimicrobial antagonism was observed with any combination. The three antimicrobial combinations were indifferent overall. The overall GM MICs of gentamicin were reduced by 2.63-, 3.80- and 1.98-fold when tested in combination with ceftriaxone, ertapenem and azithromycin, respectively. The GM MICs of the three antimicrobials by themselves were reduced by 3-, 2.57- and 1.98-fold respectively, when each was tested in combination with gentamicin. No antimicrobial antagonism was observed with any combination. ConclusionsGentamicin alone was effective in vitro against MDR N. gonorrhoeae and in combination with ceftriaxone, ertapenem or azithromycin. Combination testing of resistant strains, overall, showed lower effective MICs against gentamicin itself and each of the three antimicrobials when used in combination with gentamicin.

microbiology↗

bioRxiv2020

Susceptibility trends of zoliflodacin against multidrug-resistant Neisseria gonorrhoeae clinical isolates in NanJing, China (2014-2018)

Previously, we reported potent activity of a novel spiropyrimidinetrione, zoliflodacin, against N. gonorrhoeae isolates from symptomatic men in Nanjing, China, collected in 2013. Here, we investigated trends of susceptibilities of zoliflodacin in 986 gonococcal isolates collected from men between 2014 and 2018. N. gonorrhoeae isolates were tested for susceptibility to zoliflodacin and seven other antibiotics. Mutations in gyrA, gyrB, parC and parE genes were determined by PCR and DNA sequencing. The MIC of zoliflodacin for N. gonorrhoeae ranged from [≤]0.002 to 0.25 mg/L; the overall MIC50s and MIC90s were 0.06 mg/L and 0.125mg/L in 2018, increasing two-fold from 2014. However, the percent of isolates with lower zoliflodacin MICs declined in each year sequentially while the percent with higher MICs increased yearly (P[≤]0.00001). All isolates were susceptible to spectinomycin but resistant to ciprofloxacin (MIC [≥]1 g/ml); 21.2% (209/986) were resistant to azithromycin ([≥]1 g/ml), 43.4% (428/986) were penicillinase-producing (PPNG), 26.9% (265/986) tetracycline-resistant (TRNG) and 19.4% (191/986) were multi-drug resistant (MDR) isolates. Among 143 isolates with higher zoliflodacin MICs (0.125-0.25 mg/L), all had quinolone resistance associated double or triple mutations in gyrA; 139/143 (97.2%) also had mutations in parC. There were no D429N/A and/or K450T mutations in GyrB identified in the 143 isolates with higher zoliflodacin MICs; a S467N mutation in GyrB was identified in one isolate. We report that zoliflodacin has excellent in vitro activity against clinical gonococcal isolates, including those with high-level resistance to ciprofloxacin, azithromycin and extended spectrum cephalosporins.

microbiology↗

bioRxiv2018

Transcriptome Analysis of Neisseria gonorrhoeae During Natural Infection Reveals Differential Expression of Antibiotic Resistance Determinants Between Men and Women

Neisseria gonorrhoeae is a bacterial pathogen responsible for the sexually transmitted infection, gonorrhea. Emergence of antimicrobial resistance (AMR) of N. gonorrhoeae worldwide has resulted in limited therapeutic choices for this infection. Men who seek treatment often have symptomatic urethritis; in contrast, gonococcal cervicitis in women is usually minimally symptomatic, but may progress to pelvic inflammatory disease. Previously, we reported the first analysis of gonococcal transcriptome expression determined in secretions from women with cervical infection. Here, we defined gonococcal global transcriptional responses in urethral specimens from men with symptomatic urethritis and compared these with transcriptional responses in specimens obtained from women with cervical infections, and of in vitro-grown N. gonorrhoeae isolates. This is the first comprehensive comparison of gonococcal gene expression in infected men and women. RNA sequencing analysis revealed that 9.4% of gonococcal genes showed increased expression exclusively in men and included genes involved in host immune cell interactions and 4.3% showed increased expression exclusively in women and included phage-associated genes. Infected men and women displayed comparable antibiotic resistant-genotypes and in vitro -phenotypes, but a 4-fold higher expression of the Mtr efflux pump-related genes was observed in men. These results suggest that expression of AMR genes is programmed genotypically, and also driven by sex-specific environments. Collectively, our results indicate that distinct N. gonorrhoeae gene expression signatures are detected during genital infection in men and women. We propose that therapeutic strategies could target sex specific differences in expression of antibiotic resistance genes.

microbiology↗

bioRxiv2018

A novel sialylation site on Neisseria gonorrhoeae lipooligosaccharide links heptose II lactose expression with pathogenicity

Sialylation of lacto-W-neotetraose (LNnT) extending from heptose I (HepI) of gonococcal lipooligosaccharide (LOS) contributes to pathogenesis. Previously, gonococcal LOS sialyltransterase (Lst) was shown to sialylate LOS in Triton X-100 extracts of strain 15253, which expresses lactose from both HepI and HepII, the minimal structure required for mAb 2C7 binding. Ongoing work has shown that growth of 15253 in cytidine monophospho-W-acetylneuraminic acid (CMP-Neu5Ac)-containing media enables binding to CD33/Siglec-3, a cell surface receptor that binds sialic acid, suggesting that lactose termini on LOS of intact gonococci can be sialylated. Neu5Ac was detected on LOSs of strains 15253 and a MS11 mutant with only lactose from HepI and HepII by mass spectrometry; deleting HepII lactose rendered Neu5Ac undetectable. Resistance of HepII lactose Neu5Ac to desialylation by 2-3-specific neuraminidase suggested an 2-6-linkage. Although not associated with increased factor H binding, HepII lactose sialylation inhibited complement C3 deposition on gonococci. 15253 mutants that lacked Lst or HepII lactose were significantly attenuated in mice, confirming the importance of HepII Neu5Ac in virulence. All 75 minimally passaged clinical isolates from Nanjing, China, expressed HepII lactose, evidenced by reactivity with mAb 2C7; mAb 2C7 was bactericidal against the first 62 (of 75) isolates that had been collected sequentially and were sialylated before testing. mAb 2C7 effectively attenuated 15253 vaginal colonization in mice. In conclusion, this novel sialylation site could explain the ubiquity of gonococcal HepII lactose in vivo. Our findings reiterate the candidacy of the 2C7 epitope as a vaccine antigen and mAb 2C7 as an immunotherapeutic antibody.

microbiology↗