Invasion of HeLa cells by Providencia alcalifaciens presumably is plasmid-encoded

Magalhäes, Vera; Leal, Nilma Cintra; Melo, V.; Sobreira, Marise; Magalhães, Marcelo

doi:10.1590/s0074-02761996000600022

Cited by 6 publications

(4 citation statements)

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“…strains 205/92, 2939/90 and RMID 1656011; Table S1). Therefore it seems that the horizontal transfer of genes encoding a second T3SS on the 128kb plasmid has contributed to the emergence of enteropathogenic P. alcalifaciens strains (44, 90). Also encoded on the 128kb plasmid of P. alcalifaciens 205/92 are homologs of type III effectors known to be bacterial virulence determinants in mammalian hosts, including SptP, EspG, EspM and SipA 1a .…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, clinical strains isolated from patients with diarrhea exhibit varying invasive abilities with some P. alcalifaciens being highly invasive for human epithelial cell lines e.g. HeLa, HEp-2, Vero and Caco-2, and others being non-invasive (31,(42)(43)(44)(45)(46)(47)(48). Despite a strong association with diarrheal illness in humans and animals, a detailed understanding of the pathogenic mechanisms of P. alcalifaciens is lacking.…”

Section: Introductionmentioning

confidence: 99%

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Pathogenic diversification of the gut commensalProvidencia alcalifaciensvia acquisition of a second type III secretion system

Klein,

Predeus,

Greissl

et al. 2024

Preprint

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Providencia alcalifaciensis a Gram-negative bacterium found in a wide variety of water and land environments and organisms. It has been isolated as part of the gut microbiome of animals and insects, as well as from stool samples of patients with diarrhea. SpecificP. alcalifaciensstrains encode gene homologs of virulence factors found in other pathogenic members of the same Enterobacterales order, such asSalmonella entericaserovar Typhimurium andShigella flexneri.Whether these genes are also pathogenic determinants inP. alcalifaciensis not known. Here we have usedP. alcalifaciens205/92, a clinical isolate, within vitroandin vivoinfection models to investigateP. alcalifaciens-host interactions at the cellular level. Our particular focus was the role of two type III secretion systems (T3SS) belonging to the Inv-Mxi/Spa family. T3SS1bis widespread inProvidenciaspp. and encoded on the chromosome. T3SS1ais encoded on a large plasmid that is present in a subset ofP. alcalifaciensstrains, which are primarily isolates from diarrheal patients. Using a combination of electron and fluorescence microscopy and gentamicin protection assays we show thatP. alcalifaciens205/92 is internalized into eukaryotic cells, rapidly lyses its internalization vacuole and proliferates in the cytosol. This triggers caspase-4 dependent inflammasome responses in gut epithelial cells. The requirement for the T3SS1ain entry, vacuole lysis and cytosolic proliferation is host-cell type specific, playing a more prominent role in human intestinal epithelial cells as compared to macrophages. In a bovine ligated intestinal loop model,P. alcalifacienscolonizes the intestinal mucosa, inducing mild epithelial damage with negligible fluid accumulation. No overt role for T3SS1aor T3SS1bwas seen in the calf infection model. However, T3SS1bwas required for the rapid killing ofDrosophila melanogaster. We propose that the acquisition of two T3SS by horizontal gene transfer has allowedP. alcalifaciensto diversify its host range, from a highly virulent pathogen of insects to an opportunistic gastrointestinal pathogen of animals.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pathogenic diversification of the gut commensalProvidencia alcalifaciensvia acquisition of a second type III secretion system

Klein,

Predeus,

Greissl

et al. 2024

Preprint

View full text Add to dashboard Cite

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“…HeLa cell invasion assay showed that seven of 11 P. alcalifaciens strains isolated in the São Paulo City, Brazil, have invasive character and actin condensation ability, and no difference was observed when compared with HEp-2 cells. 30 In addition, Maszewska et al 31 demonstrated the invasive phenomenon of P. alcalifaciens in Caco-2 cell lines and compared with HEp-2 cells. The purpose of using Caco-2 cell lines was to understand the in vivo situation more closely because they can differentiate and form polarized monolayers with a phenotypical resemblance to enterocytes of the small intestine.…”

Section: Clinical Features and Diagnosismentioning

confidence: 99%

Epidemiology and Pathogenesis of Providencia alcalifaciens Infections

Shah

Odoyo

Ichinose

2019

The American Journal of Tropical Medicine and Hygiene

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Providencia alcalifaciens is a member of the family Enterobacteriaceae that has been commonly implicated as a causative agent of diarrheal infection in humans and animals. Recent outbreaks of P. alcalifaciens in both developing and developed countries have raised public health concerns. Several studies have suggested that P. alcalifaciens can cause diarrhea by invading the intestinal mucosa, although its pathogenicity has not been well established. Often routine laboratory investigations that seek etiological agents of diarrhea do not actively pursue P. alcalifaciens detection. Therefore, routine laboratory diagnosis should be given more attention for better understanding the epidemiology and pathogenicity of P. alcalifaciens.

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“…Some strains of Providencia alcalifaciens, but no strains of Providencia rettgeri or Providencia stuartii, are invasive in human cell lines (Albert et al, 1995;Janda et al, 1998;Sobreira et al, 2001;Maszewska et al, 2010). Strains of Providencia alcalifaciens isolated from diarrheal samples are able to invade several cultured mammalian cells in vitro, e.g., INT-407, HEp-2, HeLa, Vero, and Caco-2 (Guth and Perrella, 1996;Magalhaes et al, 1996;Janda et al, 1998;Murata et al, 2001;Maszewska et al, 2010). The pathogenicity of Providencia rettgeri against medflys, determined by assessing the effect of the bacteria on medfly egg hatching and development, has also been reported (Msaad Guerfali et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Comparative Genomic Analysis Reveals Genetic Mechanisms of the Variety of Pathogenicity, Antibiotic Resistance, and Environmental Adaptation of Providencia Genus

Yuan

Zhang

et al. 2020

Front. Microbiol.

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Invasion of HeLa cells by Providencia alcalifaciens presumably is plasmid-encoded

Cited by 6 publications

References 0 publications

Pathogenic diversification of the gut commensalProvidencia alcalifaciensvia acquisition of a second type III secretion system

Pathogenic diversification of the gut commensalProvidencia alcalifaciensvia acquisition of a second type III secretion system

Epidemiology and Pathogenesis of Providencia alcalifaciens Infections

Comparative Genomic Analysis Reveals Genetic Mechanisms of the Variety of Pathogenicity, Antibiotic Resistance, and Environmental Adaptation of Providencia Genus

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