Quorum sensing integrates environmental cues, cell density and cell history to control bacterial competence

Abstract

Streptococcus pneumoniae becomes competent for genetic transformation when exposed to an autoinducer peptide known as competence-stimulating peptide (CSP). This peptide was originally described as a quorum-sensing signal, enabling individual cells to regulate competence in response to population density. However, recent studies suggest that CSP may instead serve as a probe for sensing environmental cues, such as antibiotic stress or environmental diffusion. Here, we show that competence induction can be simultaneously influenced by cell density, external pH, antibiotic-induced stress, and cell history. Our experimental data is explained by a mathematical model where the environment and cell history modify the rate at which cells produce or sense CSP. Taken together, model and experiments indicate that autoinducer concentration can function as an indicator of cell density across environmental conditions, while also incorporating information on environmental factors or cell history, allowing cells to integrate cues such as antibiotic stress into their quorum-sensing response. This unifying perspective may apply to other debated quorum-sensing systems.

Antibiotic-induced cell chaining triggers pneumococcal competence by reshaping quorum sensing to autocrine signaling

“…Only when antibiotics induce competence, the ssbB promoter is activated and firefly luciferase is produced. In line with previous reports, four antibiotics belonging to the fluoroquinolone and aminoglycoside classes of antibiotics robustly induced competence ( Figure 1B) (Slager et al 2014;Prudhomme 2006;Stevens et al 2011;Moreno-Gámez et al 2017). Macrolides and linezolids classes of antibiotics were not able to induce competence (Table S1).…”

“…We selected antibiotics on basis of their use for the treatment of several pneumococcal respiratory infections (otitis media, pneumonia or exacerbations of chronic respiratory diseases), as well as for the treatment of respiratory infections with other bacterial etiologies (Table S1). Cells were grown in C+Y medium at pH 7.35, a pH non-permissive for natural competence development under our experimental conditions (Moreno-Gámez et al 2017), and antibiotics were added at concentrations below the minimum inhibitory concentration (MIC) to prevent large growth defects and cell killing. Only when antibiotics induce competence, the ssbB promoter is activated and firefly luciferase is produced.…”

“…To examine whether competence induction by AZT and CLA leads to increased horizontal gene transfer (HGT), we co-incubated two pneumococcal strains that are genetically identical except for a unique antibiotic resistance marker (tetracycline and kanamycin) integrated at different genomic locations. Since the extracellular pH is an important factor for natural competence development (Prudhomme 2006;Moreno-Gámez et al 2017;Chen & Morrison 1987), we performed this experiment in two different growth conditions (pH 7.3 and pH 7.5, nonpermissive and permissive conditions for natural competence, respectively) in presence or absence of AZT or CLA. As expected, at pH 7.3 no transformants were detected in the control condition.…”

“…One of the genes regulated by ComE, comX, encodes a sigma factor, which activates the genes required for DNA repair, DNA uptake, and transformation. CSP can be retained by producing cells (Prudhomme et al 2016), but CSP also diffuses and can induce competence in neighboring cells (Christie 2016;Havarstein et al 1995;Moreno-Gámez et al 2017). The diffusibility of the growth medium also influences competence development (Yang et al 2010).…”

“…The diffusibility of the growth medium also influences competence development (Yang et al 2010). Thus, the initiation of competence can be considered as a combination of diffusion sensing and autocrine signaling (or self-sensing) (Doğaner et al 2016;Moreno-Gámez et al 2017). The competent state is activated in response to several antibiotics, which thereby allow the bacterium to take up foreign DNA and potentially acquire antimicrobial resistance determinants (Prudhomme 2006;Slager et al 2014;Stevens et al 2011).…”