Serine Protease Autotransporters of the Enterobacteriaceae (SPATEs): Out and About and Chopping It Up

Pokharel, Pravil; Habouria, Hajer; Bessaiah, Hicham; Dozois, Charles M.

doi:10.3390/microorganisms7120594

Cited by 25 publications

(26 citation statements)

References 158 publications

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“…As of this writing, to our best knowledge this is the first report on the occurrence of the studied SPATEs in Klebsiella spp., suggesting that they potentially play an important role in the pathogenicity of Klebsiella, as previously described [52][53][54]. In addition, the sequences of SPATEs reported here are similar to those reported in other Enterobacteriaceae species as previously reported and may play the same role [52,54].…”

Section: Discussionsupporting

confidence: 88%

Klebsiella spp. cause severe and fatal disease in Mozambican children: antimicrobial resistance profile and molecular characterization

et al. 2021

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Background Klebsiella spp. are important pathogens associated with bacteremia among admitted children and is among the leading cause of death in children < 5 years in postmortem studies, supporting a larger role than previously considered in childhood mortality. Herein, we compared the antimicrobial susceptibility, mechanisms of resistance, and the virulence profile of Klebsiella spp. from admitted and postmortem children. Methods Antimicrobial susceptibility and virulence factors of Klebsiella spp. recovered from blood samples collected upon admission to the hospital (n = 88) and postmortem blood (n = 23) from children < 5 years were assessed by disk diffusion and multiplex PCR. Results Klebsiella isolates from postmortem blood were likely to be ceftriaxone resistant (69.6%, 16/23 vs. 48.9%, 43/88, p = 0.045) or extended-spectrum β-lactamase (ESBL) producers (60.9%, 14/23 vs. 25%, 22/88, p = 0.001) compared to those from admitted children. blaCTX-M-15 was the most frequent ESBL gene: 65.3%, 9/14 in postmortem isolates and 22.7% (5/22) from admitted children. We found higher frequency of genes associated with hypermucoviscosity phenotype and invasin in postmortem isolates than those from admitted children: rmpA (30.4%; 7/23 vs. 9.1%, 8/88, p = 0.011), wzi-K1 (34.7%; 8/23 vs. 8%; 7/88, p = 0.002) and traT (60.8%; 14/23 vs. 10.2%; 9/88, p < 0.0001), respectively. Additionally, serine protease auto-transporters of Enterobacteriaceae were detected from 1.8% (pic) to 12.6% (pet) among all isolates. Klebsiella case fatality rate was 30.7% (23/75). Conclusion Multidrug resistant Klebsiella spp. harboring genes associated with hypermucoviscosity phenotype has emerged in Mozambique causing invasive fatal disease in children; highlighting the urgent need for prompt diagnosis, appropriate treatment and effective preventive measures for infection control.

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Section: Discussionsupporting

confidence: 88%

Klebsiella spp. cause severe and fatal disease in Mozambican children: antimicrobial resistance profile and molecular characterization

et al. 2021

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“…Colonization of the bladder is vital for UTI pathogenesis and UPEC deploys an array of virulence factors to infect and colonize the bladder, including secreted toxins [25]. Hemolysin A [8,9], UpxA (TosA) [26], cytotoxic necrotizing factor-1 (CNF-1) [27,28], and a variety of SPATEs (serine-protease autotransporters of Enterobacteriaceae) [29] are known toxins of host cells that are produced by some UPEC strains. The recent identification of new members of the SPATEs family present in some pathogenic E. coli and their cytotoxic activity on bladder cell lines [20], led us to further investigate mechanisms underlying the cytotoxic and proteolytic activity of the TagB, TagC, and Sha SPATEs on an established human urinary bladder cell line [30,31] and other properties of these virulence-associated proteins.…”

Section: Discussionmentioning

confidence: 99%

The Serine Protease Autotransporters TagB, TagC, and Sha from Extraintestinal Pathogenic Escherichia coli Are Internalized by Human Bladder Epithelial Cells and Cause Actin Cytoskeletal Disruption

Pokharel

Díaz

Bessaiah

et al. 2020

IJMS

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TagB, TagC (tandem autotransporter genes B and C), and Sha (Serine-protease hemagglutinin autotransporter) are recently described members of the SPATE (serine protease autotransporters of Enterobacteriaceae) family. These SPATEs can cause cytopathic effects on bladder cells and contribute to urinary tract infection in a mouse model. Bladder epithelial cells form an important barrier in the urinary tract. Some SPATEs produced by pathogenic E. coli are known to breach the bladder epithelium. The capacity of these newly described SPATEs to alter bladder epithelial cells and the role of the serine protease active site were investigated. All three SPATE proteins were internalized by bladder epithelial cells and altered the distribution of actin cytoskeleton. Sha and TagC were also shown to degrade mucin and gelatin respectively. Inactivation of the serine catalytic site in each of these SPATEs did not affect secretion of the SPATEs from bacterial cells, but abrogated entry into epithelial cells, cytotoxicity, and proteolytic activity. Thus, our results show that the serine catalytic triad of these proteins is required for internalization in host cells, actin disruption, and degradation of host substrates such as mucin and gelatin.

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“…2; File S8). Notable among these were genes associated with pathogenesis in Enteroaggregative E. coli and Salmonella referred to as the Serine Protease Autotransporters of Enterobacteriaceae (SPATEs) (Pokharel et al, 2019), such as sat (13%), sigA (11%) and pic (1%). Besides, eight isolates harboured known markers of Enteropathogenic E. coli (eltAB or estA).…”

Section: Accessory Gene Content and Relationships With Other Strainsmentioning

confidence: 99%

Genomic diversity of Escherichia coli from healthy children in rural Gambia

Foster-Nyarko

Alikhan

Ikumapayi

et al. 2021

PeerJ

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Little is known about the genomic diversity of Escherichia coli in healthy children from sub-Saharan Africa, even though this is pertinent to understanding bacterial evolution and ecology and their role in infection. We isolated and whole-genome sequenced up to five colonies of faecal E. coli from 66 asymptomatic children aged three-to-five years in rural Gambia (n = 88 isolates from 21 positive stools). We identified 56 genotypes, with an average of 2.7 genotypes per host. These were spread over 37 seven-allele sequence types and the E. coli phylogroups A, B1, B2, C, D, E, F and Escherichia cryptic clade I. Immigration events accounted for three-quarters of the diversity within our study population, while one-quarter of variants appeared to have arisen from within-host evolution. Several isolates encode putative virulence factors commonly found in Enteropathogenic and Enteroaggregative E. coli, and 53% of the isolates encode resistance to three or more classes of antimicrobials. Thus, resident E. coli in these children may constitute reservoirs of virulence- and resistance-associated genes. Moreover, several study strains were closely related to isolates that caused disease in humans or originated from livestock. Our results suggest that within-host evolution plays a minor role in the generation of diversity compared to independent immigration and the establishment of strains among our study population. Also, this study adds significantly to the number of commensal E. coli genomes, a group that has been traditionally underrepresented in the sequencing of this species.

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Serine Protease Autotransporters of the Enterobacteriaceae (SPATEs): Out and About and Chopping It Up

Cited by 25 publications

References 158 publications

Klebsiella spp. cause severe and fatal disease in Mozambican children: antimicrobial resistance profile and molecular characterization

Klebsiella spp. cause severe and fatal disease in Mozambican children: antimicrobial resistance profile and molecular characterization

The Serine Protease Autotransporters TagB, TagC, and Sha from Extraintestinal Pathogenic Escherichia coli Are Internalized by Human Bladder Epithelial Cells and Cause Actin Cytoskeletal Disruption

Genomic diversity of Escherichia coli from healthy children in rural Gambia

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