A community’s survival often depends on communication between individuals, enabling them to share strategies to overcome stress and threats. Bacteria are no different. To survive in the face of their main enemy—antibiotics—bacteria have developed unique communication systems.
One such bacterium is Streptococcus pneumoniae, a major cause of severe pneumonia with high mortality that is also becoming increasingly resistant to many antibiotics. Bacteria can spread resistance by picking up and integrating helpful DNA from their environment—a process called competence— that allows them to tolerate threats and pass that ability along. But how this information is transferred throughout bacterial populations was unclear.
Now, a team led by molecular microbiologist Patrice Polard at the Centre for Integrative Biology revealed how populations of pneumococcus employ and spread competence to fend off antibiotics.1 The findings, published in Nature Communications, demonstrated that competence propagates through the population like a wave. By studying this process, scientists may discover how pneumococcus tolerates stress and develops antibiotic resistance, insights that could help researchers better manage its spread.
Polard and his team began their investigations by engineering a strain of S. pneumoniae that emits fluorescent signals when a cell becomes competent, allowing the researchers to track how the strategy unfolds across a population of cultured cells. The first few hours following treatment with a nonlethal dose of the antibiotic streptomycin were uneventful: Only a few bacterial cells became competent. But by the two-hour mark, the antibiotic-induced stress had spread through the population, and the number of cells exhibiting competence reached a critical threshold. This triggered competence in neighboring cells. Sensing danger, the competent cells rang out an alarm—likely by releasing Competence Stimulating Peptide (CSP), the molecule that triggers competence—alerting neighboring bacteria.
“The idea here is that a subtle stress could be enough to kick this thing off and promote a temporary change in a population of bacteria,” said Donald Morrison, a microbiologist at the University of Illinois Chicago who was not involved with the study.
However, not all the cells that survived the antibiotic responded in the same way: Only some of the cells underwent transformation. “This is diversifying the population,” said Polard. “You have always in the population some noncompetent cells and competent cells.” He added, “So, you will save some cells [and] you will kill the rest of the population, but in the end, it will be beneficial for the whole population.” The team suspects that this process may help bacteria survive during environmental stressors, allowing some bacteria to acquire beneficial genes while also protecting a subset of cells in the population against stress.
To determine whether competence actually helped the bacteria survive, the researchers exposed the cells to sustained treatment with DNA-damaging antibiotics. They observed that competent cells fared better than their noncompetent counterparts, exhibiting higher survival rates and greater tolerance to the drugs.
The team hypothesized that competence-driven tolerance might stem from reduced growth and altered metabolism. To test this, they focused on the competence-induced protein ComM, which slows down cell division. Genetic deletion of the ComM gene in bacteria reduced competent cells’ ability to tolerate different antibiotics, leading to increased cell death. Researchers suspect that by delaying cell division, ComM may help competent cells avoid replicating damaged DNA. Polard’s team is currently searching for other competence-activated genes that contribute to antibiotic-induced stress tolerance in pneumococcus.
Polard and his team found that antibiotics targeting other bacterial processes, like damaging the cell wall or inhibiting protein translation, also triggered widespread competence across the population. While all of the antibiotics tested in the present study showed similar effects on competent cells, the researchers are eager to explore why some antibiotics appear to be more effective against competent cells than others.
Understanding bacterial competence is not only important for unraveling bacterial evolution and adaptation but also for advancing bacterial genetics research and developing strategies to combat antibiotic resistance. “This simple discovery will explain that if you are not careful with the antibiotics, you may induce competence for a transient period and may evolve some tolerant and resistance cells,” said Polard.
“Pneumococcus has only 2,000 genes, and we don't understand enough yet about its biology, how it kills people, how it spreads,” said Morrison. Studies exploring competence provide scientists a way to investigate how these thousands of genes contribute to the spread of resistance.
- Prudhomme M, et al. Pneumococcal competence is a populational health sensor driving multilevel heterogeneity in response to antibiotics. Nat Commun. 2024;15(1):5625.
