Antibody-Mediated Serum Resistance Protects Pseudomonas aeruginosa During Bloodstream Infections

Author:

Hickson Sarah M1ORCID,Hoehensteiger Johannes K1ORCID,Mayer-Coverdale Johanna23,Torres Von Vergel L1ORCID,Feng Wenkang1,Monteith Joshua N1,Henderson Ian R4,McCarthy Kate L35,Wells Timothy J16ORCID

Affiliation:

1. Frazer Institute, Faculty of Medicine, The University of Queensland , Brisbane, Australia

2. UQ Centre for Clinical Research, The University of Queensland , Herston, Australia

3. Department of Microbiology, Pathology Queensland, Brisbane, Australia

4. Institute of Molecular Biosciences, The University of Queensland, Brisbane, Australia

5. Infectious Diseases Unit, Royal Brisbane and Women's Hospital, Brisbane, Australia

6. Australian Infectious Diseases Research Centre, The University of Queensland , Brisbane , Australia

Abstract

Abstract Background Pseudomonas aeruginosa is a frequent pathogen isolated from bacterial bloodstream infection (BSI) and is associated with high mortality. To survive in the blood, P aeruginosa must resist the bactericidal action of complement (ie, serum killing). Antibodies usually promote serum killing through the classical complement pathway; however, “cloaking antibodies” (cAbs) have been described, which paradoxically protect bacteria from serum killing. The relevance of cAbs in P aeruginosa BSI is unknown. Methods Serum and P aeruginosa were collected from a cohort of 100 patients with BSI. Isolates were tested for sensitivity to healthy control serum (HCS). cAb prevalence was determined in sera. Patient sera were mixed with HCS to determine if killing of the matched isolate was inhibited. Results Overall, 36 patients had elevated titers of cAbs, and 34 isolates were sensitive to HCS killing. Fifteen patients had cAbs and HCS-sensitive isolates; of these patients, 14 had serum that protected their matched bacteria from HCS killing. Patients with cAbs were less likely to be neutropenic or have comorbidities. Conclusions cAbs are prevalent in patients with P aeruginosa BSI and allow survival of otherwise serum-sensitive bacteria in the bloodstream. Generation of cAbs may be a risk factor for the development of BSI.

Publisher

Oxford University Press (OUP)

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