scholarly journals The QseG Lipoprotein Impacts the Virulence of EnterohemorrhagicEscherichia coliandCitrobacter rodentiumand Regulates Flagellar Phase Variation inSalmonella entericaSerovar Typhimurium

2018 ◽  
Vol 86 (4) ◽  
Author(s):  
Elizabeth A. Cameron ◽  
Charley C. Gruber ◽  
Jennifer M. Ritchie ◽  
Matthew K. Waldor ◽  
Vanessa Sperandio
Keyword(s):  
Regulatory Networks ◽  
Cultured Cells ◽  
Rabbit Model ◽  
Phase Variation ◽  
Enteric Pathogens ◽  
Infection Model ◽  
Phase Variable ◽  
Wild Type ◽  
Content Type

ABSTRACTThe QseEF histidine kinase/response regulator system modulates expression of enterohemorrhagicEscherichia coli(EHEC) andSalmonella entericaserovar Typhimurium virulence genes in response to the host neurotransmitters epinephrine and norepinephrine.qseG, which encodes an outer membrane lipoprotein, is cotranscribed withqseEFin these enteric pathogens, but there is little knowledge of its role in virulence. Here, we found that in EHEC QseG interacts with the type III secretion system (T3SS) gate protein SepL and modulates the kinetics of attaching and effacing (AE) lesion formation on tissue-cultured cells. Moreover, an EHEC ΔqseGmutant had reduced intestinal colonization in an infant rabbit model. Additionally, inCitrobacter rodentium, an AE lesion-forming pathogen like EHEC, QseG is required for full virulence in a mouse model. InS. Typhimurium, we found that QseG regulates the phase switch between the two flagellin types, FliC and FljB. In anS. Typhimurium ΔqseGmutant, the phase-variable promoter forfljBis preferentially switched into the “on” position, leading to overproduction of this phase two flagellin. In infection of tissue-cultured cells, theS. Typhimurium ΔqseGmutant provokes increased inflammatory cytokine production versus the wild type;in vivo, in a murine infection model, the ΔqseGstrain caused a more severe inflammatory response and was attenuated versus the wild-type strain. Collectively, our findings demonstrate that QseG is important for full virulence in several enteric pathogens and controls flagellar phase variation inS. Typhimurium, and they highlight both the complexity and conservation of the regulatory networks that control the virulence of enteric pathogens.

scholarly journals In VivoEfficacy of Human Simulated Regimens of Carbapenems and Comparator Agents against NDM-1-Producing Enterobacteriaceae

2013 ◽  
Vol 58 (3) ◽  
pp. 1671-1677 ◽  
Author(s):  
Dora E. Wiskirchen ◽  
Patrice Nordmann ◽  
Jared L. Crandon ◽  
David P. Nicolau
Keyword(s):  
Type Strain ◽  
Wild Type Strain ◽  
Similar Efficacy ◽  
Infection Model ◽  
High Dose ◽  
Wild Type ◽  
Prolonged Infusion ◽  
Content Type

ABSTRACTDoripenem and ertapenem have demonstrated efficacy against several NDM-1-producing isolatesin vivo, despite having high MICs. In this study, we sought to further characterize the efficacy profiles of humanized regimens of standard (500 mg given every 8 h) and high-dose, prolonged infusion of doripenem (2 g given every 8 h, 4-h infusion) and 1 g of ertapenem given intravenously every 24 h and the comparator regimens of ceftazidime at 2 g given every 8 h (2-h infusion), levofloxacin at 500 mg every 24 h, and aztreonam at 2 g every 6 h (1-h infusion) against a wider range of isolates in a murine thigh infection model. An isogenic wild-type strain and NDM-1-producingKlebsiella pneumoniaeand eight clinical NDM-1-producing members of the familyEnterobacteriaceaewere tested in immunocompetent- and neutropenic-mouse models. The wild-type strain was susceptible to all of the agents, while the isogenic NDM-1-producing strain was resistant to ceftazidime, doripenem, and ertapenem. Clinical NDM-1-producing strains were resistant to nearly all five of the agents (two were susceptible to levofloxacin). In immunocompetent mice, all of the agents produced ≥1-log10CFU reductions of the isogenic wild-type and NDM-1-producing strains after 24 h. Minimal efficacy of ceftazidime, aztreonam, and levofloxacin against the clinical NDM-1-producing strains was observed. However, despitein vitroresistance, ≥1-log10CFU reductions of six of eight clinical strains were achieved with high-dose, prolonged infusion of doripenem and ertapenem. Slight enhancements of doripenem activity over the standard doses were obtained with high-dose, prolonged infusion for three of the four isolates tested. Similar efficacy observations were noted in neutropenic mice. These data suggest that carbapenems are a viable treatment option for infections caused by NDM-1-producingEnterobacteriaceae.

scholarly journals Use of Recombinase-BasedIn VivoExpression Technology To Characterize Enterococcus faecalis Gene Expression during Infection IdentifiesIn Vivo-Expressed Antisense RNAs and Implicates the Protease Eep in Pathogenesis

2011 ◽  
Vol 80 (2) ◽  
pp. 539-549 ◽  
Author(s):  
Kristi L. Frank ◽  
Aaron M. T. Barnes ◽  
Suzanne M. Grindle ◽  
Dawn A. Manias ◽  
Patrick M. Schlievert ◽  
...  
Keyword(s):  
Enterococcus Faecalis ◽  
Rabbit Model ◽  
Microscopic Analysis ◽  
Mammalian Host ◽  
Wild Type ◽  
Antisense Transcripts ◽  
Content Type ◽  
Antisense Rnas

ABSTRACTEnterococcus faecalisis a member of the mammalian gastrointestinal microflora that has become a leading cause of nosocomial infections over the past several decades.E. faecalismust be able to adapt its physiology based on its surroundings in order to thrive in a mammalian host as both a commensal and a pathogen. We employed recombinase-basedin vivoexpression technology (RIVET) to identify promoters on theE. faecalisOG1RF chromosome that were specifically activated during the course of infection in a rabbit subdermal abscess model. The RIVET screen identified 249 putativein vivo-activated loci, over one-third of which are predicted to generate antisense transcripts. Three predicted antisense transcripts were detected inin vitro- andin vivo-grown cells, providing the first evidence ofin vivo-expressed antisense RNAs inE. faecalis. Deletions in thein vivo-activated genes that encode glutamate 5-kinase (proB[EF0038]), the transcriptional regulator EbrA (ebrA[EF1809]), and the membrane metalloprotease Eep (eep[EF2380]) did not hinder biofilm formation inin vitroassays. In a rabbit model of endocarditis, the ΔebrAstrain was fully virulent, the ΔproBstrain was slightly attenuated, and the Δeepstrain was severely attenuated. The Δeepvirulence defect could be complemented by the expression of the wild-type gene intrans. Microscopic analysis of early Δeepbiofilms revealed an abundance of small cellular aggregates that were not observed in wild-type biofilms. This work illustrates the use of a RIVET screen to provide information about the temporal activation of genes during infection, resulting in the identification and confirmation of a new virulence determinant in an important pathogen.

scholarly journals Bypassing Phase Variation of Lipooligosaccharide (LOS): Using Heptose 1 Glycan Mutants To Establish Widespread Efficacy of Gonococcal Anti-LOS Monoclonal Antibody 2C7

2019 ◽  
Vol 88 (2) ◽  
Author(s):  
Srinjoy Chakraborti ◽  
Sunita Gulati ◽  
Bo Zheng ◽  
Frank J. Beurskens ◽  
Janine Schuurman ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Polymorphonuclear Leukocytes ◽  
Phase Variation ◽  
Human Infection ◽  
Phase Variable ◽  
Content Type ◽  
Human Igg1 ◽  
And Function

ABSTRACT The sialylatable lacto-N-neotetraose (LNnT; Gal-GlcNAc-Gal-Glc) moiety from heptose I (HepI) of the lipooligosaccharide (LOS) of Neisseria gonorrhoeae undergoes positive selection during human infection. Lactose (Gal-Glc) from HepII, although phase variable, is commonly expressed in humans; loss of HepII lactose compromises gonococcal fitness in mice. Anti-LOS monoclonal antibody (MAb) 2C7, a promising antigonococcal immunotherapeutic that elicits complement-dependent bactericidal activity and attenuates gonococcal colonization in mice, recognizes an epitope comprised of lactoses expressed simultaneously from HepI and HepII. Glycan extensions beyond lactose on HepI modulate binding and function of MAb 2C7 in vitro. Here, four gonococcal LOS mutants, each with lactose from HepII but fixed (unable to phase-vary) LOS HepI glycans extended beyond the lactose substitution of HepI (lactose alone, Gal-lactose, LNnT, or GalNAc-LNnT), were used to define how HepI glycan extensions affect (i) mouse vaginal colonization and (ii) efficacy in vitro and in vivo of a human IgG1 chimeric derivative of MAb 2C7 (2C7-Ximab) with a complement-enhancing E-to-G Fc mutation at position 430 (2C7-Ximab-E430G). About 10-fold lower 2C7-Ximab-E430G concentrations achieved similar complement-dependent killing of three gonococcal mutants with glycan extensions beyond lactose-substituted HepI (lactose alone, LNnT, or GalNAc-LNnT) as 2C7-Ximab (unmodified Fc). The fourth mutant (Gal-lactose) resisted direct complement-dependent killing but was killed approximately 70% by 2C7-Ximab-E430G in the presence of polymorphonuclear leukocytes and complement. Only mutants with (sialylatable) LNnT from HepI colonized mice for >3 days, reiterating the importance of LNnT sialylation for infection. 2C7-Ximab-E430G significantly attenuated colonization caused by the virulent mutants.

scholarly journals Efficacy of Humanized Carbapenem and Ceftazidime Regimens against Enterobacteriaceae Producing OXA-48 Carbapenemase in a Murine Infection Model

2013 ◽  
Vol 58 (3) ◽  
pp. 1678-1683 ◽  
Author(s):  
Dora E. Wiskirchen ◽  
Patrice Nordmann ◽  
Jared L. Crandon ◽  
David P. Nicolau
Keyword(s):  
Wild Type Strain ◽  
Treatment Options ◽  
Infection Model ◽  
Wild Type ◽  
Content Type ◽  
Phenotypic Profile ◽  
Infection Models ◽  
The Relationship ◽  
Growth Controls

ABSTRACTEnterobacteriaceaeproducing the OXA-48 carbapenemase are emerging worldwide, leaving few treatment options. Efficacy has been demonstratedin vivowith ceftazidime against a ceftazidime-susceptible OXA-48 isolate but not with imipenem despite maintaining susceptibility. The relationship between phenotype andin vivoefficacy was assessed for OXA-48 producers using humanized regimens of 2 g doripenem every 8 h (q8h; 4 h infusion), 1 g ertapenem q24h, 2 g ceftazidime q8h (2 h inf), and 500 mg levofloxacin q24h. Each regimen was evaluated over 24 h against an isogenic pair (wild-type and OXA-48Klebsiella pneumoniaestrains) and six clinical OXA-48 isolates with and without other extended-spectrum β-lactamases in immunocompetent and neutropenic murine thigh infection models. Efficacy was determined using the change in bacterial density versus 24-h growth controls in immunocompetent studies and 0-h controls in neutropenic studies. Bacterial reductions of ≥1 log CFU were observed with all agents for the wild-type strain. Consistent with low MICs, ceftazidime and levofloxacin exhibited efficacy against the isogenic OXA-48 strain, whereas doripenem did not, despite having a susceptible MIC; no activity was observed with ertapenem, consistent with a resistant MIC. Similar trends were observed for the clinical isolates evaluated. Ceftazidime, levofloxacin, and ertapenem efficacy against isogenic and clinical OXA-48-producing strains correlated well with phenotypic profiles and pharmacodynamic targets, whereas efficacy with doripenem was variable over the MIC range studied. These data suggest that carbapenems may not be a reliable treatment for treating OXA-48 producers and add to previous observations with KPC and NDM-1 suggesting that genotype may better predict activity of the carbapenems than the phenotypic profile.

scholarly journals Pharmacodynamics of Isavuconazole in an Aspergillus fumigatus Mouse Infection Model

2015 ◽  
Vol 59 (5) ◽  
pp. 2855-2866 ◽  
Author(s):  
Seyedmojtaba Seyedmousavi ◽  
Roger J. M. Brüggemann ◽  
Jacques F. Meis ◽  
Willem J. G. Melchers ◽  
Paul E. Verweij ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Drug Exposure ◽  
Quantitative Relationship ◽  
Maximum Effect ◽  
Infection Model ◽  
Wild Type ◽  
Content Type ◽  
Type Isolate ◽  
Mouse Infection Model

ABSTRACTAzole resistance is an emerging problem inAspergillus fumigatuswhich translates into treatment failure. Alternative treatments with new azoles may improve therapeutic outcome in invasive aspergillosis (IA) even for strains with decreased susceptibility to current azoles. Thein vivoefficacy of 0.25, 1, 4, 16, 64, 128, 256, and 512 mg/kg of body weight/day prodrug isavuconazonium sulfate (BAL8557) (isavuconazole [ISA]-equivalent doses of 0.12, 0.48, 1.92, 7.68, 30.7, 61.4, 122.9, and 245.8 mg/kg/day, respectively) administered by oral gavage was assessed in an immunocompetent murine model of IA against four clinicalA. fumigatusisolates: a wild-type isolate (ISA MICEUCAST, 0.5 mg/liter) and three azole-resistant isolates harboring substitutions in thecyp51Agene: G54W (ISA MICEUCAST, 0.5 mg/liter), M220I (ISA MICEUCAST, 4 mg/liter), and TR34/L98H (ISA MICEUCAST, 8 mg/liter). The maximum effect (100% survival) was reached at a prodrug isavuconazonium sulfate dose of 64 mg/kg for the wild-type isolate, 128 mg/kg for the G54W mutant, and 256 mg/kg two times per day (q12) for the M220I mutant. A maximum response was not achieved with the TR34/L98H isolates with the highest dose of prodrug isavuconazonium sulfate (256 mg/kg q12). For a survival rate of 50%, the effective AUC0–24/MICEUCASTratio for ISA total drug was 24.73 (95% confidence interval, 22.50 to 27.18). The efficacy of isavuconazole depended on both the drug exposure and the isavuconazole MIC of the isolates. The quantitative relationship between exposure and effect (AUC0–24/MIC) can be used to optimize the treatment of human infections byA. fumigatus, including strains with decreased susceptibility.

scholarly journals In VitroandIn VivoAntimicrobial Activities of Minocycline in Combination with Azithromycin, Clarithromycin, or Tigecycline against Pythium insidiosum

2015 ◽  
Vol 60 (1) ◽  
pp. 87-91 ◽  
Author(s):  
Francielli P. K. Jesus ◽  
Érico S. Loreto ◽  
Laerte Ferreiro ◽  
Sydney H. Alves ◽  
David Driemeier ◽  
...  
Keyword(s):  
Geometric Mean ◽  
Rabbit Model ◽  
Antimicrobial Activities ◽  
Infection Model ◽  
Pythium Insidiosum ◽  
Content Type ◽  
Microdilution Method ◽  
Broth Microdilution Method

ABSTRACTThe present study investigated thein vitroand thein vivointeractions among azithromycin, clarithromycin, minocycline, and tigecycline againstPythium insidiosum.In vitroantimicrobial activities were determined by the broth microdilution method in accordance with CLSI document M38-A2, and the antibiotic interactions were assayed using the checkerboard MIC format.In vivoefficacy was determined using a rabbit infection model. The geometric mean MICs of azithromycin, clarithromycin, minocycline, and tigecycline againstP. insidiosumwere, respectively, 1.91, 1.38, 0.91, and 0.79 μg/ml. By checkerboard testing, all combinations resulted inin vitrosynergistic interactions (>60%). Antagonism was not observed. Thein vivostudies showed that azithromycin (20 mg/kg/day twice daily) alone or in combination with minocycline (10 mg/kg/day twice daily) significantly decreased the fungal burden. This study demonstrates that azithromycin possesses potent curative efficacy against subcutaneous pythiosis in the rabbit model.

scholarly journals Efficacy of Humanized Carbapenem Exposures against New Delhi Metallo-β-Lactamase (NDM-1)-Producing Enterobacteriaceae in a Murine Infection Model

2013 ◽  
Vol 57 (8) ◽  
pp. 3936-3940 ◽  
Author(s):  
Dora E. Wiskirchen ◽  
Patrice Nordmann ◽  
Jared L. Crandon ◽  
David P. Nicolau
Keyword(s):  
Maximal Activity ◽  
Bacterial Density ◽  
Infection Model ◽  
High Dose ◽  
New Delhi ◽  
Wild Type ◽  
Content Type ◽  
Immunocompetent Mice

ABSTRACTEnterobacteriaceaeproducing the novel carbapenemase New Delhi metallo-β-lactamase (NDM-1) are emerging worldwide. While these organisms often display high levels ofin vitroresistance to multiple antibiotics,in vivoefficacy data are lacking. Here, the activities of humanized ertapenem and doripenem exposures were characterized against a wild-typeK. pneumoniaeand its derived isogenic strains harboring either an NDM-1 or KPC-2 plasmid in immunocompetent mice. In addition, four clinical isolates expressing NDM-1 were evaluated. Human-simulated regimens of ertapenem at 1 g every 24 h and high-dose, prolonged infusion of doripenem at 2 g every 8 h as a 4-h infusion were evaluated over 24 h, and efficacy was determined by the change in bacterial density compared to that in 24-h growth controls. CFU reductions in bacterial density of greater than 1 log unit were observed against the wild-type strain as well as the derived isogenic NDM-1 strain, while no reduction was observed against the derived KPC-2 strain. Postexposure MICs confirmed thein vitromaintenance of the ertapenem resistance marker in both the NDM-1 and KPC-2 strains. Similar to the case for the isogenically derived NDM-1 strain, bacterial density was reduced at 24 h against all four clinical NDM-1 isolates showing variable levels of MICs for carbapenems, with near-maximal activity of both agents occurring when the doripenem MIC was ≤8 μg/ml. While carbapenem monotherapy does not appear to be an option against KPC-based infections, these data suggest that carbapenem monotherapy may be a viable option for treating NDM-1-producingEnterobacteriaceaeunder certain conditions, and this warrants furtherin vivoexploration.

scholarly journals In VivoActivities of Ceftolozane, a New Cephalosporin, with and without Tazobactam against Pseudomonas aeruginosa and Enterobacteriaceae, Including Strains with Extended-Spectrum β-Lactamases, in the Thighs of Neutropenic Mice

2012 ◽  
Vol 57 (4) ◽  
pp. 1577-1582 ◽  
Author(s):  
W. A. Craig ◽  
D. R. Andes
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Infection Model ◽  
Wild Type ◽  
Gram Negative ◽  
Content Type ◽  
Peak Dose ◽  
Extended Spectrum ◽  
The Impact ◽  
Primary Index

ABSTRACTCeftolozane is a new cephalosporin with potent activity againstPseudomonas aeruginosaandEnterobacteriaceae. A neutropenic murine thigh infection model was used to determine which pharmacokinetic/pharmacodynamic index and magnitude drives the efficacy of ceftolozane with Gram-negative bacilli, to compare the rates ofin vivokilling ofP. aeruginosaby ceftolozane and ceftazidime, and to determine the impact of different ratios of ceftolozane plus tazobactam onEnterobacteriaceaecontaining extended-spectrum β-lactamases (ESBLs). Neutropenic mice had 106.2-7.1CFU/thigh when treated with ceftolozane for 24 h with (i) various doses (3.12 to 1,600 mg/kg) and dosage intervals (3, 6, 12, and 24 h) against twoEnterobacteriaceaestrains, (ii) 0.39 to 800 mg/kg every 6 h for fourEnterobacteriaceaeand fourP. aeruginosastrains, and (iii) 400 or 800 mg/kg with 2:1. 4:1, and 8:1 ratios of tazobactam against fiveEnterobacteriaceaestrains with ESBLs. The pharmacokinetics of ceftolozane at 25, 100, and 400 mg/kg were linear with peak/dose values of 1.0 to 1.4 and half-lives of 12 to 14 min. T>MIC was the primary index driving efficacy. For stasis (1 log kill), T>MIC was 26.3% ± 2.1% (31.6% ± 1.6%) for wild-typeEnterobacteriaceae, 31.1% ± 4.9% (34.8% ± 4.4%) forEnterobacteriaceaewith ESBLs, and 24.0% ± 3.3% (31.5% ± 3.9%) forP. aeruginosa. At 200 mg/kg every 3 h, the rate ofin vivokilling ofP. aeruginosawas faster with ceftolozane than with ceftazidime (−0.34 to −0.41 log10CFU/thigh/h versus −0.21 to −0.24 log10CFU/thigh/h). The 2:1 ratio of ceftolozane with tazobactam was the most potent combination studied. The T>MIC required for ceftolozane is less than with other cephalosporins and may be due to more rapid killing.

scholarly journals Avoidance of the Host Immune System through Phase Variation in Mycoplasma pulmonis

2005 ◽  
Vol 73 (4) ◽  
pp. 2033-2039 ◽  
Author(s):  
Amy M. Denison ◽  
Brenda Clapper ◽  
Kevin Dybvig
Keyword(s):  
Immune System ◽  
Phase Variation ◽  
Surface Proteins ◽  
Tissue Tropism ◽  
Host Immune System ◽  
Phase Variable ◽  
Wild Type ◽  
Mycoplasma Pulmonis ◽  
Rag 1

ABSTRACT Phase-variable lipoproteins are commonly found in Mycoplasma species. Mycoplasma pulmonis contains a family of extensively studied phase- and size-variable lipoproteins encoded by the vsa locus. The Vsa surface proteins vary at a high frequency, the in vivo significance of which has yet to be determined. We investigated the role of Vsa phase variation in respect to tissue tropism and avoidance of the immune system in the mouse host. Mycoplasmas were cultured 3, 14, and 21 days postinoculation from the nose, lung, trachea, liver, and spleen of experimentally infected C57BL/6 (wild-type), C57BL/6-RAG-1−/− (RAG−/−), and C57BL/6-inducible nitric oxide synthase (iNOS)−/− (iNOS−/−) mice. In wild-type and iNOS−/− mice, a large number of Vsa variants were seen by 21 days postinoculation. In contrast, little Vsa variation occurred in all tissues of RAG−/− mice. Analysis of isolates from 14 days postinoculation revealed less variation of the Vsa proteins in iNOS−/− mice than in the wild type. Western blot analysis of isolates from each strain of mouse demonstrated that Vsa phase variation occurred independently of size variation, indicating no obvious selection pressure for size variants. Additionally, these experiments provided no evidence that mycoplasmas producing particular Vsa proteins adhered only to specific tissues. The data strongly indicate that Vsa phase variation is a mechanism for avoidance of the immune system with no obvious contribution to tissue tropism.

scholarly journals Identification and Characterization of theNeisseria gonorrhoeaeMscS-Like Mechanosensitive Channel

2018 ◽  
Vol 86 (6) ◽  
Author(s):  
Zhemin Wang ◽  
Xiaomin Wang ◽  
Ping Lu ◽  
Chunshan Ni ◽  
Yuezhou Li ◽  
...  
Keyword(s):  
Turgor Pressure ◽  
Bacterial Pathogen ◽  
Mechanosensitive Channel ◽  
Infection Model ◽  
Deletion Mutants ◽  
Mechanosensitive Channels ◽  
Wild Type ◽  
Content Type ◽  
Type Strains

ABSTRACTMechanosensitive channels are ubiquitous in bacteria and provide an essential mechanism to survive sudden exposure to a hypo-osmotic environment by the sensing and release of increased turgor pressure. No mechanosensitive channels have thus far been identified and characterized for the human-specific bacterial pathogenNeisseria gonorrhoeae. In this study, we identified and characterized theN. gonorrhoeaeMscS-like mechanosensitive channel (Ng-MscS). Electrophysiological analyses by the patch clamp method showed that Ng-MscS is stretch activated and contains pressure-dependent gating properties. Further mutagenesis studies of critical residues forming the hydrophobic vapor lock showed that gain-of-function mutations in Ng-MscS inhibited bacterial growth. Subsequent analysis of the function of Ng-MscS inN. gonorrhoeaeby osmotic down-shock assays revealed that the survival of Ng-mscSdeletion mutants was significantly reduced compared with that of wild-type strains, while down-shock survival was restored upon the ectopic complementation ofmscS. Finally, to investigate whether Ng-MscS is important forN. gonorrhoeaeduring infections, competition assays were performed by using a murine vaginal tract infection model. Ng-mscSdeletion mutants were outcompeted byN. gonorrhoeaewild-type strains for colonization and survival in this infection model, highlighting that Ng-MscS contributes toin vivocolonization and survival. Therefore, Ng-MscS might be a promising target for the future development of novel antimicrobials.

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