scholarly journals Binding of the RamR Repressor to Wild-Type and Mutated Promoters of theramAGene Involved in Efflux-Mediated Multidrug Resistance in Salmonella enterica Serovar Typhimurium

2011 ◽  
Vol 56 (2) ◽  
pp. 942-948 ◽  
Author(s):  
Sylvie Baucheron ◽  
Franck Coste ◽  
Sylvie Canepa ◽  
Marie-Christine Maurel ◽  
Etienne Giraud ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Dna Binding ◽  
Binding Site ◽  
Salmonella Enterica ◽  
Transcriptional Start Site ◽  
Local Level ◽  
Wild Type ◽  
Binding Model ◽  
Content Type ◽  
Serovar Typhimurium

ABSTRACTThe transcriptional activator RamA is involved in multidrug resistance (MDR) by increasing expression of the AcrAB-TolC RND-type efflux system in several pathogenicEnterobacteriaceae. InSalmonella entericaserovar Typhimurium (S.Typhimurium),ramAexpression is negatively regulated at the local level by RamR, a transcriptional repressor of the TetR family. We here studied the DNA-binding activity of the RamR repressor with theramApromoter (PramA). As determined by high-resolution footprinting, the 28-bp-long RamR binding site covers essential features of PramA, including the −10 conserved region, the transcriptional start site oframA, and two 7-bp inverted repeats. Based on the RamR footprint and on electrophoretic mobility shift assays (EMSAs), we propose that RamR interacts with PramAas a dimer of dimers, in a fashion that is structurally similar to the QacR-DNA binding model. Surface plasmon resonance (SPR) measurements indicated that RamR has a 3-fold-lower affinity (KD[equilibrium dissociation constant] = 191 nM) for the 2-bp-deleted PramAof an MDRS.Typhimurium clinical isolate than for the wild-type PramA(KD= 66 nM). These results confirm the direct regulatory role of RamR in the repression oframAtranscription and precisely define how an alteration of its binding site can give rise to an MDR phenotype.

scholarly journals Salmonella enterica Serovar Typhimurium Uses PbgA/YejM To Regulate Lipopolysaccharide Assembly during Bacteremia

2019 ◽  
Vol 88 (1) ◽  
Author(s):  
Melina B. Cian ◽  
Nicole P. Giordano ◽  
Revathi Masilamani ◽  
Keaton E. Minor ◽  
Zachary D. Dalebroux
Keyword(s):  
Salmonella Enterica ◽  
Lipid A ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Transmembrane Domain ◽  
Wild Type ◽  
Content Type ◽  
Serovar Typhimurium ◽  
Periplasmic Domain ◽  
Inner Membrane Protein ◽  
Substitution Mutations

ABSTRACT Salmonella enterica serovar Typhimurium (S. Typhimurium) relies upon the inner membrane protein PbgA to enhance outer membrane (OM) integrity and promote virulence in mice. The PbgA transmembrane domain (residues 1 to 190) is essential for viability, while the periplasmic domain (residues 191 to 586) is dispensable. Residues within the basic region (residues 191 to 245) bind acidic phosphates on polar phospholipids, like for cardiolipins, and are necessary for salmonella OM integrity. S. Typhimurium bacteria increase their OM cardiolipin concentrations during activation of the PhoPQ regulators. The mechanism involves PbgA’s periplasmic globular region (residues 245 to 586), but the biological role of increasing cardiolipins on the surface is not understood. Nonsynonymous polymorphisms in three essential lipopolysaccharide (LPS) synthesis regulators, lapB (also known as yciM), ftsH, and lpxC, variably suppressed the defects in OM integrity, rifampin resistance, survival in macrophages, and systemic colonization of mice in the pbgAΔ191–586 mutant (in which the PbgA periplasmic domain from residues 191 to 586 is deleted). Compared to the OMs of the wild-type salmonellae, the OMs of the pbgA mutants had increased levels of lipid A-core molecules, cardiolipins, and phosphatidylethanolamines and decreased levels of specific phospholipids with cyclopropanated fatty acids. Complementation and substitution mutations in LapB and LpxC generally restored the phospholipid and LPS assembly defects for the pbgA mutants. During bacteremia, mice infected with the pbgA mutants survived and cleared the bacteria, while animals infected with wild-type salmonellae succumbed within 1 week. Remarkably, wild-type mice survived asymptomatically with pbgA-lpxC salmonellae in their livers and spleens for months, but Toll-like receptor 4-deficient animals succumbed to these infections within roughly 1 week. In summary, S. Typhimurium uses PbgA to influence LPS assembly during stress in order to survive, adapt, and proliferate within the host environment.

scholarly journals An Attenuated Salmonella enterica Serovar Typhimurium Strain and Galacto-Oligosaccharides Accelerate Clearance of Salmonella Infections in Poultry through Modifications to the Gut Microbiome

2017 ◽  
Vol 84 (5) ◽  
Author(s):  
M. Andrea Azcarate-Peril ◽  
Natasha Butz ◽  
Maria Belen Cadenas ◽  
Matthew Koci ◽  
Anne Ballou ◽  
...  
Keyword(s):  
United States ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Salmonella Enterica ◽  
The United States ◽  
Wild Type ◽  
Content Type ◽  
Salmonella Infections ◽  
Serovar Typhimurium ◽  
The Impact

ABSTRACT Salmonella is estimated to cause one million foodborne illnesses in the United States every year. Salmonella -contaminated poultry products are one of the major sources of salmonellosis. Given the critical role of the gut microbiota in Salmonella transmission, a manipulation of the chicken intestinal microenvironment could prevent animal colonization by the pathogen. In Salmonella , the global regulator gene fnr ( f umarate n itrate r eduction) regulates anaerobic metabolism and is essential for adapting to the gut environment. This study tested the hypothesis that an attenuated Fnr mutant of Salmonella enterica serovar Typhimurium (attST) or prebiotic galacto-oligosaccharides (GOS) could improve resistance to wild-type Salmonella via modifications to the structure of the chicken gut microbiome. Intestinal samples from a total of 273 animals were collected weekly for 9 weeks to evaluate the impact of attST or prebiotic supplementation on microbial species of the cecum, duodenum, jejunum, and ileum. We next analyzed changes to the gut microbiome induced by challenging the animals with a wild-type Salmonella serovar 4,[5],12:r:− (Nal r ) strain and determined the clearance rate of the virulent strain in the treated and control groups. Both GOS and the attenuated Salmonella strain modified the gut microbiome but elicited alterations of different taxonomic groups. The attST produced significant increases of Alistipes and undefined Lactobacillus , while GOS increased Christensenellaceae and Lactobacillus reuteri . The microbiome structural changes induced by both treatments resulted in a faster clearance after a Salmonella challenge. IMPORTANCE With an average annual incidence of 13.1 cases/100,000 individuals, salmonellosis has been deemed a nationally notifiable condition in the United States by the Centers for Disease Control and Prevention (CDC). Earlier studies demonstrated that Salmonella is transmitted by a subset of animals (supershedders). The supershedder phenotype can be induced by antibiotics, ascertaining an essential role for the gut microbiota in Salmonella transmission. Consequently, modulation of the gut microbiota and modification of the intestinal microenvironment could assist in preventing animal colonization by the pathogen. Our study demonstrated that a manipulation of the chicken gut microbiota by the administration of an attenuated Salmonella strain or prebiotic galacto-oligosaccharides (GOS) can promote resistance to Salmonella colonization via increases of beneficial microorganisms that translate into a less hospitable gut microenvironment.

scholarly journals Engineering and Preclinical Evaluation of Attenuated Nontyphoidal Salmonella Strains Serving as Live Oral Vaccines and as Reagent Strains

2011 ◽  
Vol 79 (10) ◽  
pp. 4175-4185 ◽  
Author(s):  
Sharon M. Tennant ◽  
Jin-Yuan Wang ◽  
James E. Galen ◽  
Raphael Simon ◽  
Marcela F. Pasetti ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Lethal Dose ◽  
Invasive Disease ◽  
Oral Immunization ◽  
Oral Vaccines ◽  
Wild Type ◽  
Lethal Challenge ◽  
Antibiotic Resistant ◽  
Content Type ◽  
Serovar Typhimurium

ABSTRACTWhile nontyphoidalSalmonella(NTS) has long been recognized as a cause of self-limited gastroenteritis, it is becoming increasingly evident that multiple-antibiotic-resistant strains are also emerging as important causes of invasive bacteremia and focal infections, resulting in hospitalizations and deaths. We have constructed attenuatedSalmonella entericaserovar Typhimurium andSalmonella entericaserovar Enteritidis strains that can serve as live oral vaccines and as “reagent strains” for subunit vaccine production in a safe and economical manner. Prototype attenuated vaccine strains CVD 1921 and CVD 1941, derived from the invasive wild-type strainsS. TyphimuriumI77 andS. EnteritidisR11, respectively, were constructed by deletingguaBA, encoding guanine biosynthesis, andclpP, encoding a master protease regulator. TheclpPmutation resulted in a hyperflagellation phenotype. An additional deletion infliDyielded reagent strains CVD 1923 and CVD 1943, respectively, which export flagellin monomers. Oral 50% lethal dose (LD50) analyses showed that the NTS vaccine strains were all highly attenuated in mice. Oral immunization with CVD 1921 or CVD 1923 protected mice against lethal challenge with wild-typeS. TyphimuriumI77. Immunization with CVD 1941 but not CVD 1943 protected mice against lethal infection withS. EnteritidisR11. Immune responses induced by these strains included high levels of serum IgG anti-lipopolysaccharide (LPS) and anti-flagellum antibodies, with titers increasing progressively during the immunization schedule. SinceS. TyphimuriumandS. Enteritidisare the most common NTS serovars associated with invasive disease, these findings can pave the way for development of a highly effective, broad-spectrum vaccine against invasive NTS.

scholarly journals Overexpression of RamA, Which Regulates Production of the Multidrug Resistance Efflux Pump AcrAB-TolC, Increases Mutation Rate and Influences Drug Resistance Phenotype

2020 ◽  
Vol 64 (4) ◽  
Author(s):  
Elizabeth M. Grimsey ◽  
Natasha Weston ◽  
Vito Ricci ◽  
Jack W. Stone ◽  
Laura J. V. Piddock
Keyword(s):  
Multidrug Resistance ◽  
Mutation Rate ◽  
Selective Pressure ◽  
Efflux Pump ◽  
Transcriptional Regulators ◽  
Multidrug Resistant ◽  
Minor Role ◽  
Wild Type ◽  
Content Type ◽  
Serovar Typhimurium

ABSTRACT In Enterobacteriales, the AcrAB-TolC efflux pump exports substrates, including antimicrobials, from the cell. Overexpression of AcrAB-TolC can occur after exposure to fluoroquinolones, leading to multidrug resistance. The expression of AcrAB-TolC in Salmonella is primarily regulated by the transcriptional activator RamA. However, other transcriptional activators, such as MarA, SoxRS, and Rob, can influence AcrAB-TolC expression. This study determined whether the overproduction or absence of RamA influences the mutation rate or the phenotype of mutants selected in Salmonella enterica serovar Typhimurium SL1344 after ciprofloxacin exposure. The absence of RamA (SL1344 ramA::aph) resulted in mutation frequencies/rates similar to those of wild-type Salmonella Typhimurium SL1344. However, the overproduction of RamA (SL1344 ramR::aph) and, consequently, AcrB resulted in a significantly higher mutation frequency and rate than for wild-type Salmonella Typhimurium SL1344. Whole-genome sequencing revealed that in addition to selecting gyrA mutants resistant to quinolones, SL1344 and SL1344 ramA::aph also produced multidrug-resistant (MDR) mutants, associated with mutations in soxR. Conversely, mutations in SL1344 ramR::aph occurred in gyrA only. Although transcriptional regulators such as SoxRS are believed to play a minor role in AcrAB-TolC regulation under antibiotic selective pressure, we show that soxR mutants can be selected after exposure to ciprofloxacin, including when RamA is absent. This demonstrates that under selective pressure, Salmonella can respond to increased efflux pump expression by mutating other AcrAB-TolC regulatory genes, allowing for the evolution of MDR. Understanding how Salmonella responds to antibiotic pressure in the absence/overproduction of RamA is important if targeting transcriptional regulators to alter efflux is to be considered an avenue for future drug discovery.

scholarly journals Evidence from Mutational Analysis for a Single Transmembrane Substrate Binding Site in the Histidine ATP-Binding Cassette Transporter ofSalmonella entericaSerovar Typhimurium

2018 ◽  
Vol 201 (2) ◽  
Author(s):  
Johanna Heuveling ◽  
Heidi Landmesser ◽  
Erwin Schneider
Keyword(s):  
Binding Site ◽  
Binding Sites ◽  
Salmonella Enterica ◽  
Substrate Binding ◽  
Atp Binding ◽  
Substrate Molecule ◽  
Content Type ◽  
Charged Residues ◽  
Serovar Typhimurium ◽  
Atp Binding Cassette

ABSTRACTThe histidine ATP-binding cassette (ABC) transporter ofSalmonella entericaserovar Typhimurium is among the best-studied type I ABC import systems. The transporter consists of two transmembrane subunits, HisQ and HisM, and a homodimer of the nucleotide-binding subunit, HisP. Substrates are delivered by two periplasmic solute binding proteins, HisJ and LAO, with preferences for histidine and for lysine, arginine, and ornithine, respectively. A homology model was built by using the arginine-bound crystal structure of the closely related Art(QN)2transporter ofThermoanaerobacter tengcongensisas the template. In the homodimeric Art(QN)2, one substrate molecule is bound to each of the ArtQ subunits, whereas the structural model and sequence alignments predict only one substrate molecule in contact with HisM. To address the question whether one or two binding sites exist in heterodimeric HisQM, we have studied the functional consequences of mutations by monitoring (i) the complementation of growth ond-histidine of auxotrophic tester strains, (ii) the growth of tester strains on arginine as a nitrogen source, and (iii) ATPase activity of purified variants in a lipid environment. Our results demonstrate that two negatively charged residues, namely, HisM-E166 and HisQ-D61, are indispensable for function. Furthermore, the complete reconstruction of an ArtQ-like binding site in HisQ resulted in an inactive transporter. Likewise, switching the positions of both negatively charged residues between HisQ and HisM caused transport-deficient phenotypes. Thus, we propose that one substrate molecule is primarily liganded by residues of HisM while HisQ-D61 forms a crucial salt bridge with the α-amino group of the substrate.IMPORTANCECanonical ATP-binding cassette (ABC) importers are major players in the translocation of numerous nutrients, vitamins, and growth factors to the cytoplasm of prokaryotes. Moreover, some ABC importers have been identified as virulence factors in bacterial pathogenesis. Thus, a full understanding of their mode of action is considered a prerequisite, among others, for the development of novel antibacterial drugs. However, mainly owing to the lack of structural information, the knowledge of the chemical nature and number of substrate binding sites formed by the transmembrane subunits of ABC importers is scarce. Here, we provide evidence from mutational analyses that, in contrast to homologous homodimeric systems, the heterodimeric histidine transporter ofSalmonella entericaserovar Typhimurium is liganding only one substrate molecule between its transmembrane subunits, HisM and HisQ.

scholarly journals Corrected Genome Annotations Reveal Gene Loss and Antibiotic Resistance as Drivers in the Fitness Evolution of Salmonella enterica Serovar Typhimurium

2016 ◽  
Vol 198 (23) ◽  
pp. 3152-3161 ◽  
Author(s):  
Sandip Paul ◽  
Evgeni V. Sokurenko ◽  
Sujay Chattopadhyay
Keyword(s):  
Multidrug Resistance ◽  
Salmonella Enterica ◽  
Gene Loss ◽  
Bacterial Genome ◽  
Genomic Islands ◽  
Genomic Diversity ◽  
Content Type ◽  
Chromosomal Genes ◽  
Serovar Typhimurium ◽  
Genome Annotations

ABSTRACT Horizontal acquisition of novel chromosomal genes is considered to be a key process in the evolution of bacterial pathogens. However, the identification of gene presence or absence could be hindered by the inconsistencies in bacterial genome annotations. Here, we performed a cross-annotation of omnipresent core and mosaic accessory genes in the chromosome of Salmonella enterica serovar Typhimurium across a total of 20 fully assembled genomes deposited into GenBank. Cross-annotation resulted in a 32% increase in the number of core genes and a 3-fold decrease in the number of genes identified as mosaic genes (i.e., genes present in some strains only) by the original annotation. Of the remaining noncore genes, the vast majority were prophage genes, and 255 of the nonphage genes were actually of core origin but lost in some strains upon the emergence of the S . Typhimurium serovar, suggesting that the chromosomal portion of the S . Typhimurium genome acquired a very limited number of novel genes other than prophages. Only horizontally acquired nonphage genes related to bacterial fitness or virulence were found in four recently sequenced isolates, all located on three different genomic islands that harbor multidrug resistance determinants. Thus, the extensive use of antimicrobials could be the main selection force behind the new fitness gene acquisition and the emergence of novel Salmonella pathotypes. IMPORTANCE Significant discrepancies in the annotations of bacterial genomes could mislead the conclusions about evolutionary origin of chromosomal genes, as we demonstrate here via a cross-annotation-based analysis of Salmonella Typhimurium genomes from GenBank. We conclude that despite being able to infect a broad range of vertebrate hosts, the genomic diversity of S . Typhimurium strains is almost exclusively limited to gene loss and the transfer of prophage DNA. Only nonphage chromosomal genes acquired after the emergence of the serovar are linked to the genomic islands harboring multidrug resistance factors. Since the fitness factors could lead to increased virulence, this poses an important research question: could overuse or misuse of antimicrobials act as selection forces for the emergence of more pathogenic strains of Salmonella ?

scholarly journals Novel DNA Binding and Regulatory Activities for σ54 (RpoN) in Salmonella enterica Serovar Typhimurium 14028s

2017 ◽  
Vol 199 (12) ◽  
Author(s):  
Ashley C. Bono ◽  
Christine E. Hartman ◽  
Sina Solaimanpour ◽  
Hao Tong ◽  
Steffen Porwollik ◽  
...  
Keyword(s):  
Dna Binding ◽  
Binding Sites ◽  
Salmonella Enterica ◽  
Environmental Changes ◽  
Atp Hydrolysis ◽  
Content Type ◽  
Dna Binding Sites ◽  
A Genome ◽  
Serovar Typhimurium ◽  
Host Microbe Interactions

ABSTRACT The variable sigma (σ) subunit of the bacterial RNA polymerase (RNAP) holoenzyme, which is responsible for promoter specificity and open complex formation, plays a strategic role in the response to environmental changes. Salmonella enterica serovar Typhimurium utilizes the housekeeping σ70 and five alternative sigma factors, including σ54. The σ54-RNAP differs from other σ-RNAP holoenzymes in that it forms a stable closed complex with the promoter and requires ATP hydrolysis by an activated cognate bacterial enhancer binding protein (bEBP) to transition to an open complex and initiate transcription. In S. Typhimurium, σ54-dependent promoters normally respond to one of 13 different bEBPs, each of which is activated under a specific growth condition. Here, we utilized a constitutively active, promiscuous bEBP to perform a genome-wide identification of σ54-RNAP DNA binding sites and the transcriptome of the σ54 regulon of S. Typhimurium. The position and context of many of the identified σ54 RNAP DNA binding sites suggest regulatory roles for σ54-RNAP that connect the σ54 regulon to regulons of other σ factors to provide a dynamic response to rapidly changing environmental conditions. IMPORTANCE The alternative sigma factor σ54 (RpoN) is required for expression of genes involved in processes with significance in agriculture, bioenergy production, bioremediation, and host-microbe interactions. The characterization of the σ54 regulon of the versatile pathogen S. Typhimurium has expanded our understanding of the scope of the σ54 regulon and how it links to other σ regulons within the complex regulatory network for gene expression in bacteria.

scholarly journals Use of Attenuated but Metabolically Competent Salmonella as a Probiotic To Prevent or Treat Salmonella Infection

2016 ◽  
Vol 84 (7) ◽  
pp. 2131-2140 ◽  
Author(s):  
Anice Sabag-Daigle ◽  
Henry M. Blunk ◽  
Juan F. Gonzalez ◽  
Brandi L. Steidley ◽  
Prosper N. Boyaka ◽  
...  
Keyword(s):  
Typhoid Fever ◽  
Salmonella Enterica ◽  
Probiotic Bacterium ◽  
Wild Type ◽  
Nutrient Source ◽  
Content Type ◽  
Nutrient Sources ◽  
Novel Approach ◽  
Serovar Typhimurium ◽  
Utilization Pathway

Salmonella entericais among the most burdensome of foodborne disease agents. There are over 2,600 serovars that cause a range of disease manifestations ranging from enterocolitis to typhoid fever. While there are two vaccines in use in humans to protect against typhoid fever, there are none that prevent enterocolitis. If vaccines preventing enterocolitis were to be developed, they would likely protect against only one or a few serovars. In this report, we tested the hypothesis that probiotic organisms could compete for the preferred nutrient sources ofSalmonellaand thus prevent or treat infection. To this end, we added thefralocus, which encodes a utilization pathway for theSalmonella-specific nutrient source fructose-asparagine (F-Asn), to the probiotic bacteriumEscherichia coliNissle 1917 (Nissle) to increase its ability to compete withSalmonellain mouse models. We also tested a metabolically competent, but avirulent,Salmonella entericaserovar Typhimurium mutant for its ability to compete with wild-typeSalmonella. The modified Nissle strain became more virulent and less able to protect againstSalmonellain some instances. On the other hand, the modifiedSalmonellastrain was safe and effective in preventing infection with wild-typeSalmonella. While we tested for efficacy only againstSalmonellaTyphimurium, the modifiedSalmonellastrain may be able to compete metabolically with most, if not all,Salmonellaserovars, representing a novel approach to control of this pathogen.

scholarly journals Salmonella Gene rma (ramA) and Multiple-Drug-Resistant Salmonella enterica Serovar Typhimurium

2004 ◽  
Vol 48 (6) ◽  
pp. 2292-2294 ◽  
Author(s):  
Tahar van der Straaten ◽  
Riny Janssen ◽  
Dik J. Mevius ◽  
Jaap T. van Dissel
Keyword(s):  
Escherichia Coli ◽  
Multidrug Resistance ◽  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Multiple Drug ◽  
Drug Resistant ◽  
Wild Type ◽  
Antibiotic Susceptibilities ◽  
Multiple Drug Resistant ◽  
Serovar Typhimurium

ABSTRACT MarA and its homologue, RamA, have been implicated in multidrug resistance (MDR). RamA overexpression in Salmonella enterica serovar Typhimurium and Escherichia coli conferred MDR independently of marA. Inactivation of ramA did not affect the antibiotic susceptibilities of wild-type S. enterica serovar Typhimurium or 15 unrelated clinical MDR isolates. Thus, ramA overexpression is not a common MDR mechanism in Salmonella.

scholarly journals Palmitoylation State Impacts Induction of Innate and Acquired Immunity by the Salmonella enterica Serovar TyphimuriummsbBMutant

2011 ◽  
Vol 79 (12) ◽  
pp. 5027-5038 ◽  
Author(s):  
Qingke Kong ◽  
David A. Six ◽  
Qing Liu ◽  
Lillian Gu ◽  
Kenneth L. Roland ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Lipid A ◽  
Inflammatory Responses ◽  
Outer Membrane Proteins ◽  
Acyl Chain ◽  
Wild Type ◽  
Proinflammatory Response ◽  
Content Type ◽  
Serovar Typhimurium

ABSTRACTLipopolysaccharide (LPS), composed of lipid A, core, and O-antigen, is a major virulence factor ofSalmonella entericaserovar Typhimurium, with lipid A being a major stimulator to induce the proinflammatory response via the Toll-like receptor 4 (TLR4)-MD2-CD14 pathway. WhileSalmonella msbBmutants lacking the myristate chain in lipid A were investigated widely as an anticancer vaccine, inclusion of themsbBmutation in aSalmonellavaccine to deliver heterologous antigens has not yet been investigated. We introduced themsbBmutation alone or in combination with mutations in other lipid A acyl chain modification genes encoding PagL, PagP, and LpxR into wild-typeS. entericaserovar Typhimurium. ThemsbBmutation reduced virulence, while thepagL,pagP, andlpxRmutations did not affect virulence in themsbBmutant background when administered orally to BALB/c mice. Also, all mutants exhibited sensitivity to polymyxin B but did not display sensitivity to deoxycholate. LPS derived frommsbBmutants induced less inflammatory responses in human Mono Mac 6 and murine macrophage RAW264.7 cellsin vitro. However, anmsbBmutant did not decrease the induction of inflammatory responses in mice compared to the levels induced by the wild-type strain, whereas anmsbB pagPmutant induced less inflammatory responsesin vivo. The mutations were moved to an attenuatedSalmonellavaccine strain to evaluate their effects on immunogenicity. Lipid A modification caused by themsbBmutation alone and in combination withpagL,pagP, andlpxRmutations led to higher IgA production in the vaginal tract but still retained the same IgG titer level in serum to PspA, a test antigen fromStreptococcus pneumoniae, and to outer membrane proteins (OMPs) fromSalmonella.

Sign in / Sign up

Export Citation Format

Share Document