scholarly journals Loss of Multicellular Behavior in Epidemic African Nontyphoidal Salmonella enterica Serovar Typhimurium ST313 Strain D23580

mBio ◽  
2016 ◽  
Vol 7 (2) ◽  
Author(s):  
Larissa A. Singletary ◽  
Joyce E. Karlinsey ◽  
Stephen J. Libby ◽  
Jason P. Mooney ◽  
Kristen L. Lokken ◽  
...  
Keyword(s):  
Stress Resistance ◽  
Salmonella Enterica ◽  
Genomic Analysis ◽  
Bloodstream Infections ◽  
Host Adaptation ◽  
Sub Saharan Africa ◽  
Loss Of Function ◽  
Serovar Typhimurium ◽  
Mode Of Transmission ◽  
Sub Saharan

ABSTRACT Nontyphoidal Salmonella enterica serovar Typhimurium is a frequent cause of bloodstream infections in children and HIV-infected adults in sub-Saharan Africa. Most isolates from African patients with bacteremia belong to a single sequence type, ST313, which is genetically distinct from gastroenteritis-associated ST19 strains, such as 14028s and SL1344. Some studies suggest that the rapid spread of ST313 across sub-Saharan Africa has been facilitated by anthroponotic (person-to-person) transmission, eliminating the need for Salmonella survival outside the host. While these studies have not ruled out zoonotic or other means of transmission, the anthroponotic hypothesis is supported by evidence of extensive genomic decay, a hallmark of host adaptation, in the sequenced ST313 strain D23580. We have identified and demonstrated 2 loss-of-function mutations in D23580, not present in the ST19 strain 14028s, that impair multicellular stress resistance associated with survival outside the host. These mutations result in inactivation of the KatE stationary-phase catalase that protects high-density bacterial communities from oxidative stress and the BcsG cellulose biosynthetic enzyme required for the RDAR (red, dry, and rough) colonial phenotype. However, we found that like 14028s, D23580 is able to elicit an acute inflammatory response and cause enteritis in mice and rhesus macaque monkeys. Collectively, these observations suggest that African S . Typhimurium ST313 strain D23580 is becoming adapted to an anthroponotic mode of transmission while retaining the ability to infect and cause enteritis in multiple host species. IMPORTANCE The last 3 decades have witnessed an epidemic of invasive nontyphoidal Salmonella infections in sub-Saharan Africa. Genomic analysis and clinical observations suggest that the Salmonella strains responsible for these infections are evolving to become more typhoid-like with regard to patterns of transmission and virulence. This study shows that a prototypical African nontyphoidal Salmonella strain has lost traits required for environmental stress resistance, consistent with an adaptation to a human-to-human mode of transmission. However, in contrast to predictions, the strain remains capable of causing acute inflammation in the mammalian intestine. This suggests that the systemic clinical presentation of invasive nontyphoidal Salmonella infections in Africa reflects the immune status of infected hosts rather than intrinsic differences in the virulence of African Salmonella strains. Our study provides important new insights into the evolution of host adaptation in bacterial pathogens.

scholarly journals An African Salmonella Typhimurium ST313 sublineage with extensive drug-resistance and signatures of host adaptation

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Sandra Van Puyvelde ◽  
Derek Pickard ◽  
Koen Vandelannoote ◽  
Eva Heinz ◽  
Barbara Barbé ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Bloodstream Infections ◽  
Host Adaptation ◽  
Sub Saharan Africa ◽  
Major Health ◽  
Extensive Drug Resistance ◽  
Serovar Typhimurium ◽  
Republic Of The Congo ◽  
Sub Saharan ◽  
Genetic Signatures

Abstract Bloodstream infections by Salmonella enterica serovar Typhimurium constitute a major health burden in sub-Saharan Africa (SSA). These invasive non-typhoidal (iNTS) infections are dominated by isolates of the antibiotic resistance-associated sequence type (ST) 313. Here, we report emergence of ST313 sublineage II.1 in the Democratic Republic of the Congo. Sublineage II.1 exhibits extensive drug resistance, involving a combination of multidrug resistance, extended spectrum β-lactamase production and azithromycin resistance. ST313 lineage II.1 isolates harbour an IncHI2 plasmid we name pSTm-ST313-II.1, with one isolate also exhibiting decreased ciprofloxacin susceptibility. Whole genome sequencing reveals that ST313 II.1 isolates have accumulated genetic signatures potentially associated with altered pathogenicity and host adaptation, related to changes observed in biofilm formation and metabolic capacity. Sublineage II.1 emerged at the beginning of the 21st century and is involved in on-going outbreaks. Our data provide evidence of further evolution within the ST313 clade associated with iNTS in SSA.

scholarly journals The role of a single non-coding nucleotide in the evolution of an epidemic African clade of Salmonella

2017 ◽  
Author(s):  
Disa L. Hammarlöf ◽  
Carsten Kröger ◽  
Siân V. Owen ◽  
Rocío Canals ◽  
Lizeth Lacharme Lora ◽  
...  
Keyword(s):  
Gene Expression Signature ◽  
Systemic Infection ◽  
Bloodstream Infections ◽  
Human Infection ◽  
Sub Saharan Africa ◽  
Infection Model ◽  
Nucleotide Polymorphisms ◽  
Bacterial Survival ◽  
Serovar Typhimurium ◽  
Sub Saharan

Introductory ParagraphSalmonella enterica serovar Typhimurium ST313 is a relatively newly emerged sequence type that is causing a devastating epidemic of bloodstream infections across sub-Saharan Africa. Analysis of hundreds of Salmonella genomes has revealed that ST313 is closely-related to the ST19 group of S. Typhimurium that cause gastroenteritis across the world. The core genomes of ST313 and ST19 vary by just 1000 single-nucleotide polymorphisms (SNPs). We hypothesised that the phenotypic differences that distinguish African Salmonella from ST19 are caused by certain SNPs that directly modulate the transcription of virulence genes.Here we identified 3,597 transcriptional start sites (TSS) of the ST313 strain D23580, and searched for a gene expression signature linked to pathogenesis of Salmonella. We identified a SNP in the promoter of the pgtE gene that caused high expression of the PgtE virulence factor in African S. Typhimurium, increased the degradation of the factor B component of human complement, contributed to serum resistance and modulated virulence in the chicken infection model. The PgtE protease is known to mediate systemic infection in animal models. We propose that high levels of expression PgtE of by African S. Typhimurium ST313 promotes bacterial survival and bacterial dissemination during human infection.Our finding of a functional role for an extra-genic SNP shows that approaches used to deduce the evolution of virulence in bacterial pathogens should include a focus on non-coding regions of the genome.

scholarly journals Role of a single noncoding nucleotide in the evolution of an epidemic African clade of Salmonella

2018 ◽  
Vol 115 (11) ◽  
pp. E2614-E2623 ◽  
Author(s):  
Disa L. Hammarlöf ◽  
Carsten Kröger ◽  
Siân V. Owen ◽  
Rocío Canals ◽  
Lizeth Lacharme-Lora ◽  
...  
Keyword(s):  
Gene Expression Signature ◽  
Bloodstream Infections ◽  
Human Infection ◽  
Sub Saharan Africa ◽  
Infection Model ◽  
Bacterial Survival ◽  
Phenotypic Differences ◽  
Serovar Typhimurium ◽  
Sub Saharan ◽  
Transcriptional Start Sites

Salmonella enterica serovar Typhimurium ST313 is a relatively newly emerged sequence type that is causing a devastating epidemic of bloodstream infections across sub-Saharan Africa. Analysis of hundreds of Salmonella genomes has revealed that ST313 is closely related to the ST19 group of S. Typhimurium that cause gastroenteritis across the world. The core genomes of ST313 and ST19 vary by only ∼1,000 SNPs. We hypothesized that the phenotypic differences that distinguish African Salmonella from ST19 are caused by certain SNPs that directly modulate the transcription of virulence genes. Here we identified 3,597 transcriptional start sites of the ST313 strain D23580, and searched for a gene-expression signature linked to pathogenesis of Salmonella. We identified a SNP in the promoter of the pgtE gene that caused high expression of the PgtE virulence factor in African S. Typhimurium, increased the degradation of the factor B component of human complement, contributed to serum resistance, and modulated virulence in the chicken infection model. We propose that high levels of PgtE expression by African S. Typhimurium ST313 promote bacterial survival and dissemination during human infection. Our finding of a functional role for an extragenic SNP shows that approaches used to deduce the evolution of virulence in bacterial pathogens should include a focus on noncoding regions of the genome.

scholarly journals Draft Genome Sequences of 11 Salmonella enterica Serovar Typhimurium Strains Isolated from Human Systemic and Nonsystemic Sites in Brazil

2018 ◽  
Vol 6 (5) ◽  
Author(s):  
Pedro Henrique N. Panzenhagen ◽  
Narayan C. Paul ◽  
Carlos A. Conte Junior ◽  
Renata G. Costa ◽  
Dália P. Rodrigues ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Draft Genome ◽  
Sequence Type ◽  
Sub Saharan Africa ◽  
Genome Sequences ◽  
Serovar Typhimurium ◽  
Sub Saharan

ABSTRACT Salmonella enterica serovar Typhimurium strains isolated from systemic sites outside sub-Saharan Africa have been rarely sequenced. Here, we report the draft genome sequences of S . Typhimurium sequence type 19 (ST19) ( n = 9), ST1649 ( n = 1), and ST313 ( n = 1) strains isolated from human systemic (e.g., blood) and nonsystemic (e.g., stool and wounds) sites in Brazil.

scholarly journals Genes Required for the Fitness of Salmonella enterica Serovar Typhimurium during Infection of Immunodeficientgp91−/−phoxMice

2016 ◽  
Vol 84 (4) ◽  
pp. 989-997 ◽  
Author(s):  
Andrew J. Grant ◽  
Olusegun Oshota ◽  
Roy R. Chaudhuri ◽  
Matthew Mayho ◽  
Sarah E. Peters ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Insertion Site ◽  
Sub Saharan Africa ◽  
Relative Fitness ◽  
Wild Type ◽  
Content Type ◽  
Immunodeficient Mice ◽  
Serovar Typhimurium ◽  
Sub Saharan ◽  
Bacterial Genes

Salmonella entericacauses systemic diseases (typhoid and paratyphoid fever), nontyphoidal septicemia (NTS), and gastroenteritis in humans and other animals worldwide. An important but underrecognized emerging infectious disease problem in sub-Saharan Africa is NTS in children and immunocompromised adults. A current goal is to identifySalmonellamutants that are not pathogenic in the absence of key components of the immune system such as might be found in immunocompromised hosts. Such attenuated strains have the potential to be used as live vaccines. We have used transposon-directed insertion site sequencing (TraDIS) to screen mutants ofSalmonella entericaserovar Typhimurium for their ability to infect and grow in the tissues of wild-type and immunodeficient mice. This was to identify bacterial genes that might be deleted for the development of live attenuated vaccines that would be safer to use in situations and/or geographical areas where immunodeficiencies are prevalent. The relative fitness of each of 9,356 transposon mutants, representing mutations in 3,139 different genes, was determined ingp91−/−phoxmice. Mutations in certain genes led to reduced fitness in both wild-type and mutant mice. To validate these results, these genes were mutated by allelic replacement, and resultant mutants were retested for fitness in the mice. A defined deletion mutant ofcysEwas attenuated in C57BL/6 wild-type mice and immunodeficientgp91−/−phoxmice and was effective as a live vaccine in wild-type mice.

scholarly journals Refined Live Attenuated Salmonella enterica Serovar Typhimurium and Enteritidis Vaccines Mediate Homologous and Heterologous Serogroup Protection in Mice

2015 ◽  
Vol 83 (12) ◽  
pp. 4504-4512 ◽  
Author(s):  
Sharon M. Tennant ◽  
Patrick Schmidlein ◽  
Raphael Simon ◽  
Marcela F. Pasetti ◽  
James E. Galen ◽  
...  
Keyword(s):  
Vaccine Efficacy ◽  
Salmonella Enterica ◽  
Developed Countries ◽  
Sub Saharan Africa ◽  
Lethal Challenge ◽  
Major Health Problem ◽  
Content Type ◽  
Serovar Typhimurium ◽  
Sub Saharan ◽  
Group B

Invasive nontyphoidalSalmonella(NTS) infections constitute a major health problem among infants and toddlers in sub-Saharan Africa; these infections also occur in infants and the elderly in developed countries. We genetically engineered aSalmonella entericaserovar Typhimurium strain of multilocus sequence type 313, the predominant genotype circulating in sub-Saharan Africa. We evaluated the capacities ofS. Typhimurium andSalmonella entericaserovar Enteritidis ΔguaBAΔclpXlive oral vaccines to protect mice against a highly lethal challenge dose of the homologous serovar and determined protection against other group B and D serovars circulating in sub-Saharan Africa. The vaccinesS. Typhimurium CVD 1931 andS. Enteritidis CVD 1944 were immunogenic and protected BALB/c mice against 10,000 50% lethal doses (LD50) ofS. Typhimurium orS. Enteritidis, respectively.S. Typhimurium CVD 1931 protected mice against the group B serovarSalmonella entericaserovar Stanleyville (91% vaccine efficacy), andS. Enteritidis CVD 1944 protected mice against the group D serovarSalmonella entericaserovar Dublin (85% vaccine efficacy). High rates of survival were observed when mice were infected 12 weeks postimmunization, indicating that the vaccines elicited long-lived protective immunity. Whereas CVD 1931 did not protect againstS. Enteritidis R11, CVD 1944 did mediate protection againstS. Typhimurium D65 (81% efficacy). These findings suggest that a bivalent (S. Typhimurium andS. Enteritidis) vaccine would provide broad protection against the majority of invasive NTS infections in sub-Saharan Africa.

scholarly journals Ceftriaxone-Resistant Salmonella enterica Serotype Typhimurium Sequence Type 313 from Kenyan Patients Is Associated with theblaCTX-M-15Gene on a Novel IncHI2 Plasmid

2015 ◽  
Vol 59 (6) ◽  
pp. 3133-3139 ◽  
Author(s):  
Samuel Kariuki ◽  
Chinyere Okoro ◽  
John Kiiru ◽  
Samuel Njoroge ◽  
Geoffrey Omuse ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Bloodstream Infections ◽  
Developed Countries ◽  
Multidrug Resistant ◽  
Sub Saharan Africa ◽  
Resistant Bacteria ◽  
Content Type ◽  
Class 1 ◽  
Genes Encoding ◽  
Sub Saharan

ABSTRACTMultidrug-resistant bacteria pose a major challenge to the clinical management of infections in resource-poor settings. Although nontyphoidalSalmonella(NTS) bacteria cause predominantly enteric self-limiting illness in developed countries, NTS is responsible for a huge burden of life-threatening bloodstream infections in sub-Saharan Africa. Here, we characterized nineS. Typhimurium isolates from an outbreak involving patients who initially failed to respond to ceftriaxone treatment at a referral hospital in Kenya. TheseSalmonella entericaserotype Typhimurium isolates were resistant to ampicillin, chloramphenicol, cefuroxime, ceftriaxone, aztreonam, cefepime, sulfamethoxazole-trimethoprim, and cefpodoxime. Resistance to β-lactams, including to ceftriaxone, was associated with carriage of a combination ofblaCTX-M-15,blaOXA-1, andblaTEM-1genes. The genes encoding resistance to heavy-metal ions were borne on the novel IncHI2 plasmid pKST313, which also carried a pair of class 1 integrons. All nine isolates formed a single clade withinS. Typhimurium ST313, the major clone of an ongoing invasive NTS epidemic in the region. This emerging ceftriaxone-resistant clone may pose a major challenge in the management of invasive NTS in sub-Saharan Africa.

scholarly journals A GMMA-CPS-Based Vaccine for Non-Typhoidal Salmonella

Vaccines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 165
Author(s):  
Akosiererem S. Sokaribo ◽  
Sumudu R. Perera ◽  
Zoe Sereggela ◽  
Ryan Krochak ◽  
Lindsay R. Balezantis ◽  
...  
Keyword(s):  
Vaccine Development ◽  
Random Mutagenesis ◽  
Bloodstream Infections ◽  
Sub Saharan Africa ◽  
Colanic Acid ◽  
High Fatality Rate ◽  
Current Vaccine ◽  
Membrane Antigens ◽  
Human Use ◽  
Sub Saharan

Non-typhoidal Salmonella are a major cause of gastroenteritis worldwide, as well as causing bloodstream infections in sub-Saharan Africa with a high fatality rate. No vaccine is currently available for human use. Current vaccine development strategies are focused on capsular polysaccharides (CPS) present on the surface of non-typhoidal Salmonella. This study aimed to boost the amount of CPS purified from S. Typhimurium for immunization trials. Random mutagenesis with Tn10 transposon increased the production of CPS colanic acid, by 10-fold compared to wildtype. Immunization with colanic acid or colanic acid conjugated to truncated glycoprotein D or inactivated diphtheria toxin did not induce a protective immune response in mice. However, immunization with Generalized Modules for Membrane Antigens (GMMAs) isolated from colanic acid overproducing isolates reduced Salmonella colonization in mice. Our results support the development of a GMMA-CPS-based vaccine against non-typhoidal Salmonella.

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