Social behaviour involving drug resistance: the role of initial density, initial frequency and population structure in shaping the effect of antibiotic resistance as a public good

• Published in: Heredity Vol. 119; no. 5; pp. 295 - 301
• Main Authors: Domingues, I L, Gama, J A, Carvalho, L M, Dionisio, F
• Format: Journal Article
• Language: English
• Published: England Springer Nature B.V 01.11.2017; Nature Publishing Group
• Subjects: Amides; Ampicillin; Ampicillin - pharmacology; Antibiotic resistance; Antibiotics; Bacteria; beta-Lactamases - genetics; Cell density; Coculture Techniques; Coding; Demographics; Drug resistance; Drug Resistance, Microbial - genetics; E coli; Escherichia coli - drug effects; Escherichia coli - genetics; Genetic Fitness; Original; Pathogens; Penicillin; Plasmids; Plasmids - genetics; Population Density; Population structure; Producer cells; Social behavior; Social factors; Social interactions; Virulence; Virulence factors; β-Lactam antibiotics
• ISSN: 0018-067X; 1365-2540; 1365-2540
• DOI: 10.1038/hdy.2017.33

Bacteria sometimes cooperate with co-inhabiting cells. Pathogenic bacteria, for example, often produce and excrete virulence factors, eventually benefitting both producer and non-producer cells. The role of social interactions involving antibiotic resistance, however, has been more elusive. Enzymes that inactivate β-lactam antibiotics such as ampicillin or penicillin (β-lactamases) are good candidates as public goods. Nonetheless, it has been claimed that bacteria harbouring plasmids of natural origin coding for β-lactamase almost do not protect sensitive bacteria. This does not fit with the fact that ampicillin-sensitive bacteria can be isolated from subjects undergoing ampicillin treatment. We hypothesised that there are two non-exclusive explanations for the discrepancy between previous works: (1) the range of values of demographic conditions (such as initial strain frequency, initial total cell density or habitat structure) has not been broad enough to include most scenarios, or (2) there are interactions between some of these factors. We performed experiments with Escherichia coli bacterial cells to measure the degree of protection of sensitive cells when co-cultured with cells harbouring RP4, R16a or the R1 plasmids, all of natural origin and coding for β-lactamases, and in presence of ampicillin. In these co-cultures, performed in structured and non-structured environments, both the initial total cell density and the initial frequency of sensitive cells spanned four orders of magnitude. We found protection of sensitive cells in 63% of tested conditions. All factors (plasmid, structure, frequency and density) significantly affect levels of protection. Moreover, all factors interact, with interactions revealing large or very large effect sizes.