Murine monoclonal antibody elicited with antibiotic-exposed Escherichia coli exerts protective capacity in experimental bacterial infections

Lun, Maria Teresa; Amatucci, Aldo; Raponi, Giammarco; Filadoro, F; Bartolazzi, Armando; Fraioli, Rocco; Natali, Pier Giorgio; Mancini, Carlo

doi:10.1099/00222615-41-3-179

Cited by 4 publications

(13 citation statements)

References 16 publications

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“…The results of the present study confirmed that MAbs MT1F and ARM1-4, elicited in mice after immunisation with antibiotic-treated E. coli O6:K À , offered full protection against lethal challenge with E. coli O6:K À and a certain degree of cross-protection against lethal challenge with different E. coli serotypes [19,20]. When the MAbs were administered together, the crossprotective capacity was significantly improved.…”

Section: Discussionsupporting

confidence: 83%

“…Both MAbs were of the IgG1 isotype. MT1F reacted with a polypeptide of 12 kDa [19] and ARM1-4 with polypeptides of 30 and 40 kDa [20] in the untreated E. coli O6:K À .…”

Section: Mabsmentioning

confidence: 99%

“…The enhanced protection was transferred to normal mice by sera from mice immunised with antibiotic-treated bacteria, thus suggesting a key role for antibodies. In further studies, several MAbs were produced from the spleens of BALB=c mice immunised with E. coli O6:K À pre-exposed to antibiotic [19,20]. The MAbs identified protein epitopes on the surface of the untreated E. coli, were able to activate complement and gave protection against lethal challenge with homologous and, to a certain degree, against heterologous E. coli serotypes [19,20].…”

Section: Introductionmentioning

confidence: 99%

“…Murine MAbs MT1F and ARM1-4 were produced and purified by protein G chromatography as reported previously [19,20]. To elicit the MAbs, the mice had been immunised with E. coli O6:K À grown overnight in the presence of 0:5 3 MIC of aztreonam (BristolMyers Squibb, Rome, Italy) and then killed with formalin [22].…”

Section: Mabsmentioning

confidence: 99%

“…However, despite the attractive simplicity of this approach, it is still controversial and data regarding the existence of such cross-reactive antibodies and the nature of the target epitopes are conflicting [14,15]. A different approach was based on the observation that antibodies to outer-membrane proteins (OMPs) were found to be protective in experimentally-induced infections [16][17][18][19][20][21].…”

Section: Introductionmentioning

confidence: 99%

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Protective features of monoclonal antibodies to Escherichia coli during experimental infection of mice with homologous and heterologous serotypes of E. coli

Raponi¹,

Ghezzi²,

Lun³

et al. 2000

Journal of Medical Microbiology

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Murine monoclonal antibodies (MAbs) MT1F and ARM1-4, recognising proteins on the surface of untreated Escherichia coli O6:K 2 , protected 100% of mice challenged intraperitoneally with 2 3 LD50 of the same strain. MAb MT1F protected 70% of animals challenged with 2 3 LD50 of E. coli O111:B4, whereas ARM1-4 gave complete protection. Lower survival was observed in mice given either MAb and challenged with E. coli O128:K 2 , with values ranging from 30 to 42%. However, the protection afforded against E. coli O111:B4 and E. coli O128:K 2 was significantly improved when the mice were pre-treated with a mixture of the two MAbs. Control mice, pre-treated with unrelated ascitic fluid and challenged with any of the E. coli serotypes, showed 100% mortality and organ histological lesions resembling those of the early stages of septic shock. The mice had high levels of circulating endotoxin and tumour necrosis factor-AE (TNF-AE) at 90 min after challenge. In contrast, mice treated with MAbs and surviving the infection displayed moderate histological lesions, enhanced bacterial clearance and lower serum levels of TNF-AE, despite circulating endotoxin levels that were higher than in the control group. Protection by the MAbs was probably due to the prevention of the bacterial spread to organs and of the cascade of events leading to septic shock. This occurred in spite of the presence of high levels of circulating endotoxin.

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Section: Discussionsupporting

confidence: 83%

“…Both MAbs were of the IgG1 isotype. MT1F reacted with a polypeptide of 12 kDa [19] and ARM1-4 with polypeptides of 30 and 40 kDa [20] in the untreated E. coli O6:K À .…”

Section: Mabsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Mabsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Protective features of monoclonal antibodies to Escherichia coli during experimental infection of mice with homologous and heterologous serotypes of E. coli

Raponi¹,

Ghezzi²,

Lun³

et al. 2000

Journal of Medical Microbiology

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The Escherichia coli TolC efflux pump protein is immunogenic and elicits protective antibodies

Silva,

Teixeira,

Costa

et al. 2024

Journal of Leukocyte Biology

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Antimicrobial resistance is an increasing worldwide public health burden that threatens to make existent antimicrobials obsolete. An important mechanism of antimicrobial resistance is the overexpression of efflux pumps, which reduce the intracellular concentration of antimicrobials. TolC is the outer membrane protein of an efflux pump that has gained attention as a therapeutic target. Little is known about the immune response against TolC. Here we evaluated the immune response against TolC from Escherichia coli. TolC in silico epitope prediction showed several residues that could bind to human antibodies, and we showed that human plasma presented higher titers of anti-TolC IgG and IgA, than IgM. E. coli recombinant TolC protein stimulated macrophages in vitro to produce nitric oxide, as well as IL-6 and TNF-α, assessed by Griess assay and ELISA, respectively. Immunization of mice with TolC intraperitoneally and an in vitro re-stimulation led to increased T cell proliferation and IFNγ production, evaluated by flow cytometry and ELISA, respectively. TolC mouse immunization stimulated anti-TolC IgM and IgG production, with higher levels of IgG1 and IgG2, amongst the IgG subclasses. Anti-TolC murine antibodies could bind to live E. coli and increase bacterial uptake and elimination by macrophages in vitro. Intraperitoneal or intranasal, but not oral, immunizations with inactivated E. coli also led to anti-TolC antibody production. Finally, TolC immunization increased mouse survival rates to antimicrobial-sensitive or resistant E. coli infection. Our results showed that TolC is immunogenic, leading to the production of protective antibodies against E. coli, reinforcing its value as a therapeutic target.

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Characterisation and protective capacity of monoclonal antibodies elicited in mice against protein epitopes of antibiotic-exposed Escherichia coli

Lun

Raponi²,

Amatucci³

et al. 1997

Journal of Medical Microbiology

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Murine monoclonal antibody elicited with antibiotic-exposed Escherichia coli exerts protective capacity in experimental bacterial infections

Cited by 4 publications

References 16 publications

Protective features of monoclonal antibodies to Escherichia coli during experimental infection of mice with homologous and heterologous serotypes of E. coli

Protective features of monoclonal antibodies to Escherichia coli during experimental infection of mice with homologous and heterologous serotypes of E. coli

The Escherichia coli TolC efflux pump protein is immunogenic and elicits protective antibodies

Characterisation and protective capacity of monoclonal antibodies elicited in mice against protein epitopes of antibiotic-exposed Escherichia coli

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