Summary When cooperation is critical for survival, cheating can lead to population collapse. One mechanism of cooperation that permits the coexistence of cooperators and cheaters is an impure public good, whose public benefits are shared, but with a private benefit retained by the cooperator. It has yet to be determined how the contributions of the public and private benefit affect population survival. Using simulations and experiments with β‐lactamase‐expressing bacteria, we found that for a given amount of public and private benefit, the population was most sensitive to collapse when initiated from an intermediate fraction of cooperators due to the near‐concurrent collapse of the cooperator and cheater populations. We found that increasing the ratio of public to private benefit increased sensitivity to collapse. A low ratio allowed cooperators to survive on their private benefit after the public benefit could not rescue the cheaters. A high ratio allowed the cheaters to survive to high concentrations of ampicillin due to the high public benefit. However, small increases in ampicillin caused a rapid decline in the entire population as the private benefit was insufficient to allow self‐rescue of the cooperators. Our findings have implications in the persistence of populations that rely on cooperation for survival.

Most bacteria exist and interact within polymicrobial communities. These interactions produce unique compounds, increase virulence and augment antibiotic resistance. One community associated with negative healthcare outcomes consists of Pseudomonas aeruginosa and Staphylococcus aureus. When co-cultured, virulence factors secreted by P. aeruginosa reduce metabolism and growth in S. aureus. When grown in vitro, this allows P. aeruginosa to drive S. aureus toward extinction. However, when found in vivo, both species can co-exist. Previous work has noted that this may be due to altered gene expression or mutations. However, little is known about how the growth environment could influence the co-existence of both species. Using a combination of mathematical modeling and experimentation, we show that changes to bacterial growth and metabolism caused by differences in the growth environment can determine the final population composition. We found that changing the carbon source in growth media affects the ratio of ATP to growth rate for both species, a metric we call absolute growth. We found that as a growth environment increases the absolute growth for one species, that species will increasingly dominate the co-culture. This is due to interactions between growth, metabolism, and metabolism-altering virulence factors produced by P. aeruginosa. Finally, we show that the relationship between absolute growth and the final population composition can be perturbed by altering the spatial structure in the community. Our results demonstrate that differences in growth environment can account for conflicting observations regarding the co-existence of these bacterial species in the literature, provides support for the intermediate disturbance hypothesis, and may offer a novel mechanism to manipulate polymicrobial populations.

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Background Hemophilus influenzae is a gram-negative coccobacillus. Non-typeable H. influenzae infection is a significant cause of disease that activates the inflammatory pathway involving the nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome. A gain-of-function mutation in NLRP3 results in cryopyrin-associated periodic syndromes characterized by inflammatory conditions in the lungs, skin, joints, and eyes but not in the gut. This leads to homeostasis of the gut microbiota, which reduces inflammation and may have protective effect against colorectal cancer (CRC). This study aimed to evaluate the correlation between H. influenzae infection and the incidence of CRC. Methods A retrospective study was conducted from 2010 to 2019 using a HIPAA-compliant national database. ICD-10, ICD-9, CPT, and National Drug Codes were used to identify patients with or without a history of H. influenzae infection. Standard statistical methods were used to analyze the outcomes. Results The query was analyzed and matched, resulting in 13,610 patients in both groups. The incidence of CRC was 167 and 446 in the H. influenzae and control groups, respectively. The difference was statistically significant with P < 2.2 ×10 -16 and an odds ratio of 0.41 (95% confidence interval: 0.36 - 0.47). Additionally, the groups were further evaluated and matched by treatment, which resulted in a statistically significant decrease in CRC incidence in the H. influenzae group. Conclusion This study showed a statistically significant correlation between H. influenzae and the reduced incidence of CRC. This reduction in CRC in patients with a history of H. influenzae infection suggests a potential link to the NLRP3 inflammasome, which should be further studied.

Most bacteria exist and interact within polymicrobial communities. These interactions produce unique compounds, increased virulence and augmented antibiotic resistance. One community associated with negative healthcare outcomes consists of Pseudomonas aeruginosa and Staphylococcus aureus. When co-cultured, virulence factors secreted by P. aeruginosa reduce metabolism and growth in S. aureus. When grown in vitro this allows P. aeruginosa to drive S. aureus towards extinction. However, when found in vivo, both species can co-exist. Previous work has noted that this may due to altered gene expression or mutations. However, little is known about how the growth environment could influence co-existence of both species. Using a combination of mathematical modeling and experimentation, we show that changes to bacterial growth and metabolism caused by differences in the growth environment can determine final population composition. We found that changing the carbon source in growth medium affects the ratio of ATP to growth rate for both species, a metric we call absolute growth. We found that as a growth environment increases absolute growth for one species, that species will dominate the co- culture. This is due to interactions between growth, metabolism and metabolism altering virulence factors produced by P. aeruginosa. Finally, we show that the relationship between absolute growth and final population composition can be perturbed by altering the spatial structure in the community. Our results demonstrate that differences in growth environment can account for conflicting observations regarding the co-existence of these bacterial species in the literature, and may offer a novel mechanism to manipulate polymicrobial populations.