Pic-Producing Escherichia coli Induces High Production of Proinflammatory Mediators by the Host Leading to Death by Sepsis

Dutra, Itaynara L.; Araújo, Lorena G.; Assunção, Raissa Guará; Lima, Yago A.; Nascimento, Johnny Ramos do; Vale, André Álvares Marques; Alves, Patrícia Costa Santos; Trovão, Liana O.; Santos, Ana Maria Ribeiro dos; Silva, Rosa Maria; Silva, Lucilene A.; Maciel, Márcia C.G.; Sousa, Eduardo Martins de; Elias, Waldir P.; Nascimento, Flávia R.F.; Abreu, Afonso G.

doi:10.3390/ijms21062068

Cited by 9 publications

(5 citation statements)

References 56 publications

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“…A similar result was observed by Dutra et al. ( 82 ) when the ExPEC strain F5, a Pic-producing ExPEC, and its respective pic mutant were tested in a murine sepsis model. While all animals infected with the wild type strain died, all animals infected with the mutant strain survived, suggesting that Pic is also involved in the pathogenesis of sepsis.…”

Section: Discussionsupporting

confidence: 85%

Secreted Autotransporter Toxin (Sat) Mediates Innate Immune System Evasion

et al. 2022

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Several strategies are used by Escherichia coli to evade the host innate immune system in the blood, such as the cleavage of complement system proteins by secreted proteases. Members of the Serine Proteases Autotransporters of Enterobacteriaceae (SPATE) family have been described as presenting proteolytic effects against complement proteins. Among the SPATE-encoding genes sat (secreted autotransporter toxin) has been detected in high frequencies among strains of E. coli isolated from bacteremia. Sat has been characterized for its cytotoxic action, but the possible immunomodulatory effects of Sat have not been investigated. Therefore, this study aimed to evaluate the proteolytic effects of Sat on complement proteins and the role in pathogenesis of BSI caused by extraintestinal E. coli (ExPEC). E. coli EC071 was selected as a Sat-producing ExPEC strain. Whole-genome sequencing showed that sat sequences of EC071 and uropathogenic E. coli CFT073 present 99% identity. EC071 was shown to be resistant to the bactericidal activity of normal human serum (NHS). Purified native Sat was used in proteolytic assays with proteins of the complement system and, except for C1q, all tested substrates were cleaved by Sat in a dose and time-dependent manner. Moreover, E. coli DH5α survived in NHS pre-incubated with Sat. EC071-derivative strains harboring sat knockout and in trans complementations producing either active or non-active Sat were tested in a murine sepsis model. Lethality was reduced by 50% when mice were inoculated with the sat mutant strain. The complemented strain producing active Sat partially restored the effect caused by the wild-type strain. The results presented in this study show that Sat presents immunomodulatory effects by cleaving several proteins of the three complement system pathways. Therefore, Sat plays an important role in the establishment of bloodstream infections and sepsis.

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Section: Discussionsupporting

confidence: 85%

Secreted Autotransporter Toxin (Sat) Mediates Innate Immune System Evasion

et al. 2022

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“…Another study from Universidade Ceuma in Brazil showed decreased survival rate of infected mice up to 34% during 12 hours period after intraperitoneal injection of E. coli and 100% mortality after 24 hours [27]. In this study, the survival rate of mice in positive control group decreased into 55.6% 12 hours after bacteria injection and after 18 hours post injection, the survival rate was 11.1%.…”

Section: Figuresupporting

confidence: 51%

Antibacterial activity of Piper betle ethanolic extract against ESBL producing Escherichia coli in sepsis induced BALB/c mice

Dzulkarnain¹,

Ratridewi²,

Hantoko³

et al. 2021

GSC Biol. and Pharm. Sci.

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Sepsis is an organ dysfunction caused by dysregulation of immune response towards systemic infection with high incidence and mortality rate. Innovative breakthrough is required to manage sepsis especially extended spectrum beta lactamase (ESBL) producing Escherichia coli (E. coli) induced sepsis. Utilization of Piper betle extract to manage sepsis could be considered as an alternative therapy and should be proven scientifically so meropenem utilization could be reduced. This study aimed to evaluate the antimicrobial effect of Piper betle ethanolic extract in BALB/c mice infected with ESBL producing E. coli. We identified terpene, apiol, polyphenol, eugenol, myristicin, flavonoid, safrole, lynalil acetate, and allyl tetramethoxy benzene in the Piper betle ethanolic extract using thin layer chromatography. The minimum inhibitory concentration of the Piper betle ethanolic extract against ESBL producing E. coli was 3 mg/mL assessed using broth dilution method. We evaluated the effect of Piper betle ethanolic extract to the survival rate of BALB/c mice infected with ESBL producing E. coli. The single dose administration of Piper betle ethanolic extract prolonged the survival rate of the infected BALB/c mice for 6 hours.

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“…In addition, ExPEC VFs, which were involved in human ExPEC infections, such as urinary tract infections, sepsis, and meningitis, were also highly identified in ESBL/AmpC-EC than in the non-ESBL/ AmpC-EC (p < 0.05). Especially, the prevalence of the three VFs, namely papC, pic, and ompT, which were reported to show a positive association with the high mortality in human ExPEC infection (Kudinha et al, 2013;Krawczyk et al, 2015;Dutra et al, 2020), was significantly higher in the ESBL/ AmpC-EC isolates (p < 0.05). Furthermore, the OR of biofilm formation was 3.8-fold greater (95% CI: 1.42-10.30, p < 0.05) in the ESBL/AmpC-EC isolates than in the non-ESBL/ AmpC-EC isolates.…”

Section: Discussionmentioning

confidence: 94%

Prevalence, Characteristics and Clonal Distribution of Extended-Spectrum β-Lactamase- and AmpC β-Lactamase-Producing Escherichia coli Following the Swine Production Stages, and Potential Risks to Humans

Lee

Guk

et al. 2021

Front. Microbiol.

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The worldwide spread of extended spectrum β-lactamase (ESBL)- and AmpC β-lactamase (AmpC)-producing Escherichia coli poses serious threats to public health. Swine farms have been regarded as important reservoirs of ESBL/AmpC-EC. This study aimed to determine the prevalence, ESBL/AmpC types, and clonal distribution of ESBL/AmpC-EC from swine farms and analyze the difference according to the swine production stages. In addition, we evaluated the potential risks of swine ESBL/AmpC-EC clones to humans. Individual fecal samples (n = 292) were collected from weaning, growing, finishing, and pregnant pigs in nine swine farms of South Korea between July 2017 and March 2020. In total, 161 ESBL/AmpC-EC isolates were identified (55.1%), with the highest prevalence detected in the weaning stage (86.3%). The dominant ESBL and AmpC types were CTX-M-55 (69.6%) and CMY-2 (4.3%), respectively. CTX-M found in all production stages, while CMY was only found in growing and finishing stages. In the conjugation assay, the high transferability of CTX-M gene (55.8%) was identified, while the transfer of CMY gene was not identified. The major clonal complexes (CCs) were CC101-B1 (26.8%), CC10-A (8.7%), and CC648-F (2.9%). There was similarity in clonal distribution between different swine production stages within swine farms, estimated using the k-means analysis, which suggested a clonal transmission between the different swine stages. Among swine ESBL/AmpC-EC sequence types (STs), seven STs (ST101, ST10, ST648, ST457, ST410, ST617, and ST744) were common with the human ESBL/AmpC-EC, which registered in National Center for Biotechnology Information database. The clonal population structure analysis based on the virulence factor (VF) presented that swine ESBL/AmpC-EC clones, especially ST101-B1, harbored a highly virulent profile. In conclusion, ESBL/AmpC-EC was distributed throughout the swine production stages, with the highest prevalence in the weaning stage. The CTX-M was present in all stages, while CMY was mostly found in growing-finishing stages. The swine ESBL/AmpC-EC was identified to harbor shared clone types with human ESBL/AmpC-EC and a virulent profile posing potential risk to humans. Considering the possibility of genetic and clonal distribution of ESBL/AmpC-EC among swine production stages, this study suggests the need for strategies considering the production system to control the prevalence of ESBL/AmpC-EC in swine farms.

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Pic-Producing Escherichia coli Induces High Production of Proinflammatory Mediators by the Host Leading to Death by Sepsis

Cited by 9 publications

References 56 publications

Secreted Autotransporter Toxin (Sat) Mediates Innate Immune System Evasion

Secreted Autotransporter Toxin (Sat) Mediates Innate Immune System Evasion

Antibacterial activity of Piper betle ethanolic extract against ESBL producing Escherichia coli in sepsis induced BALB/c mice

Prevalence, Characteristics and Clonal Distribution of Extended-Spectrum β-Lactamase- and AmpC β-Lactamase-Producing Escherichia coli Following the Swine Production Stages, and Potential Risks to Humans

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