A Mathematical Model of Exoprotein Production in Bacteria

Coleman, K.; Fowler, A. C.

doi:10.1093/imammb/1.1.77

Cited by 3 publications

(3 citation statements)

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“…Another possible explanation for this discrepancy is that K S is actually much higher than in the model, approaching or even exceeding 1% nutrient. Because this is far higher than values typically observed for bacteria (21,23), this explanation seems less likely.…”

Section: Resultsmentioning

confidence: 66%

“…Prior theoretical studies of microbial growth on macromolecular substrates have typically assumed either a constant output of secreted proteases per unit biomass or a constant fraction of nutrient influx devoted to secreted proteases under nutrient-limited growth conditions (21,(24)(25)(26). Our study suggests that a more complex mode of regulation of secreted proteases is required to capture the natural physiological regulation of secreted products for P. aeruginosa.…”

Section: Discussionmentioning

confidence: 85%

“…The doubling time is ≈30 min, yielding μ max = (ln 2)/ 30 min, which is ≈0.023 min . K S is difficult to measure (20,21), especially for a nutrient source such as caseinolytic peptides, which are not homogeneous and whose average composition could change over the course of PA14 growth in casein. We used a K S value of 0.01 mass % based on preliminary data fitting.…”

Section: Resultsmentioning

confidence: 99%

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Investment in secreted enzymes during nutrient-limited growth is utility dependent

Cezairliyan

Ausubel

2017

Proc. Natl. Acad. Sci. U.S.A.

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Pathogenic bacteria secrete toxins and degradative enzymes that facilitate their growth by liberating nutrients from the environment. To understand bacterial growth under nutrient-limited conditions, we studied resource allocation between cellular and secreted components by the pathogenic bacterium Pseudomonas aeruginosa during growth on a protein substrate that requires extracellular digestion by secreted proteases. We identified a quantitative relationship between the rate of increase of cellular biomass under nutrient-limiting growth conditions and the rate of increase in investment in secreted proteases. Production of secreted proteases is stimulated by secreted signals that convey information about the utility of secreted proteins during nutrient-limited growth. Growth modeling using this relationship recapitulated the observed kinetics of bacterial growth on a protein substrate. The proposed regulatory strategy suggests a rationale for quorum-sensing-dependent stimulation of the production of secreted enzymes whereby investment in secreted enzymes occurs in proportion to the utility they confer. Our model provides a framework that can be applied toward understanding bacterial growth in many environments where growth rate is limited by the availability of nutrients.bacterial growth modeling | resource allocation | polymeric nutrient acquisition | extracellular protease production | quorum sensing N utrient acquisition is essential for the proliferation of all forms of life. Organic nutrients such as amino acids, nucleic acids, and sugars are often present in the environment as large oligomers that must be partially digested outside the cell to be imported. Many bacteria are capable of secreting hydrolytic enzymes that perform these functions. Secreted enzymes play critical roles in many microbe-associated processes including pathogenesis, as digestion and uptake of nutrients are essential for a pathogen to proliferate within a host (1-6).How do bacteria regulate the production of enzymes involved in degradation of extracellular macromolecules? We do not understand bacterial growth kinetics in environments with polymeric nutrient sources despite over a century of research on bacterial growth because the regulation of secreted hydrolytic enzyme production is not well understood (7). Production of many secreted proteins is affected by the production and sensing of secreted small molecules called autoinducers in a diverse group of processes known as quorum sensing. Disruption of quorum-sensing systems often inhibits the production of secreted proteins, resulting in the inability to metabolize extracellular nutrients (8,9). Although the qualitative reliance of secreted enzymes on quorum sensing is well established, a quantitative understanding of the relationship between bacterial growth and protein secretion is lacking.We sought to understand how bacteria regulate investment in secreted enzymes by studying growth of the ubiquitous bacterial pathogen Pseudomonas aeruginosa in a medium where nutrient acquisition ...

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Section: Resultsmentioning

confidence: 66%