The Selective Advantage of the lac Operon for Escherichia coli Is Conditional on Diet and Microbiota Composition

Abstract

The lac operon is one of the best known gene regulatory circuits and constitutes a landmark example of how bacteria tune their metabolism to nutritional conditions. It is nearly ubiquitous in Escherichia coli strains justifying the use of its phenotype, the ability to consume lactose, for species identification. Lactose is the primary sugar found in milk, which is abundant in mammals during the first weeks of life. However, lactose is virtually non-existent after the weaning period, with humans being an exception as many consume dairy products throughout their lives. The absence of lactose during adulthood in most mammals and the rarity of lactose in the environment, means that the selective pressure for maintaining the lac operon could be weak for long periods of time. Despite the ability to metabolize lactose being a hallmark of E. coli’s success when colonizing its primary habitat, the mammalian intestine, the selective value of this trait remains unknown in this ecosystem during adulthood. Here we determine the competitive advantage conferred by the lac operon to a commensal strain of E. coli when colonizing the mouse gut. We find that its benefit, which can be as high as 11%, is contingent on the presence of lactose in the diet and on the presence of other microbiota members in the gut, but the operon is never deleterious. These results help explaining the pervasiveness of the lac operon in E. coli, but also its polymorphism, as lac-negative E. coli strains albeit rare can naturally occur in the gut.

An in vitro analysis of how lactose modifies the gut microbiota structure and function of adults in a donor-independent manner

“…These data suggested that lactose treatment selected for taxa capable of expressing the β-galactosidase enzyme and able to metabolize this compound, thereby providing a nutritional, competitive advantage. This hypothesis was supported by the results of a previous study on Escherichia coli which found that the presence of the lac operon, which carries the β-galactosidase gene, provided a competitive advantage for this taxon to colonize the intestines of mice when lactose was supplied as a nutrient source ( 21 ). Additionally, it was previously reported that lactase non-persistent humans consuming dietary lactose had increased fecal β-galactosidase activity and lowered fecal pH, which pointed toward an increase in acid-tolerant, lactose utilizing taxa, such as lactic acid bacteria Lactobacillus , and Bifidobacterium ( 22 , 45 , 46 ).…”

“…In the colon, a large proportion of gut microbes have the genetic capacity to produce their own β-galactosidase enzyme and are therefore able to hydrolyze lactose, utilize the resulting monosaccharides, and produce byproducts such as lactate, short-chain fatty acids (SCFAs), H 2 , CO 2 , and CH 4 ( 21 , 22 ). Based on this information, it is a reasonable hypothesis that the consumption of lactose may impact the composition and metabolome of the gut microbiota.…”

Relationship between Desiccation Tolerance and Biofilm Formation in Shiga Toxin-Producing Escherichia coli

“…However, we later confirmed these colonies as E. coli through PCR amplification. LMG agar contains lactose as a carbon source and the lac operon is one of the best-known gene regulatory circuits, exemplifying how bacteria adapt their metabolism to nutritional conditions [ 32 ]. Stressors that disrupt the lac operon could have led to the changes in colony color.…”

Hybrid de novo Genome Assembly of Erwinia sp. E602 and Bioinformatic Analysis Characterized a New Plasmid-Borne lac Operon Under Positive Selection

“…The lac operon is a hallmark gene of the regulatory circuit for bacteria to regulate metabolism according to nutrient conditions in the environment (Leonard et al, 2015;Malakar, 2015;Karkare et al, 2021;Pinto et al, 2021). Through genome function annotation, a large number of genes related to lactose metabolism were found in Erwinia sp.…”

“…In the presence of lactose, the lac repressor is released from the operon to allow RNA transcription ( Marbach and Bettenbrock, 2012 ). Notably, the lac operon confers a competitive advantage for bacterial survival in the environments ( Pinto et al, 2021 ). Therefore, the study of lac operon in the newly identified strain Erwinia sp.…”