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Effect of inherent immunity factors on development of antibiotic tolerance and survival of bacterial populations under antibiotic attack

2015/11/01 by Е. В. Демкина, E. V. Demkina, Н. Г. Лойко +13
Biochemistry, Genetics and Molecular Biology · #Antibiotic Resistance in Bacteria #Bacterial Genetics and Biotechnology #Bacterial biofilms and quorum sensing

paper · doi:10.1134/s0026261715060028

crossref issued 2015/11/01 · crossref published 2015/11/01 · crossref published-print 2015/11/01 · openalex publication_date 2015/11/01 · crossref created 2015/11/23 · crossref published-online 2015/11/25 · openalex created_date 2025/10/10 · crossref deposited 2026/03/29 · crossref indexed 2026/07/24 · openalex updated_date 2026/07/31

Abstract

Effect of human inherent immunity factors of, a gene-encoded antibacterial peptide indolicidin (Ind) and a cytokine interleukin 1 (IL1) on formation of antibiotic-tolerant persister cells surviving in the presence of ciprofloxacin (Cpf, 100 μg/mL) and ampicillin (Amp, 100 μg/mL) in submerged bacterial cultures (Staphylococcus aureus FGA 209P, Escherichia coli K12, and Pseudomonas aeruginosa PAO1) was studied. While Ind in physiological concentrations (0.3 and 3.0 μg/mL) introduced to the lag- or exponential-phase cultures of test organisms exhibited no reliable effect on population growth, the number of persisters increased at 3.0 μg/mL. Bactericidal Ind concentrations (9 μg/mL) suppressed S. aureus growth (-0.1% of surviving cells) with subsequent recovery due to development of the more antibiotic-tolerant white variant. Treatment with Cpf after Ind addition resulted in mutual potentiation of their antimicrobial activity, with the number of S. aureus persisters 2 to 3 orders of magnitude lower than in the case of the antibiotic alone. IL1, another immunity factor, when introduced (0.1-1 ng/mL) to the exponentially growing S. aureus culture (but not to the lag phase culture) had a temporary growth-static effect, with the number of persisters surviving Cpf treatment (100 μg/mL) increasing by 1 to 2 orders of magnitude. Electron microscopy revealed significant alterations in the outer cell envelope layer of surviving S. aureus cells, which should be associated with their changed antigenic properties. Thus, the factors of human inherent immunity have a dose-dependent effect on the growth of bacterial populations. In combination with antibiotics, they exhibit synergism of antimicrobial action (indolicidin) and minimize (indolicidin) or increase (interleukin 1) the frequency of formation of persister cells responsible for survival of a population subjected to an antibiotic attack.

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