Biology subjects

Domingues, C. P. F.

Publications and source records attributed to Domingues, C. P. F..

3 recordsLinked to original sources

bioRxiv2025

Conjugative Plasmids Rarely Confer Antibiotic Resistance or Virulence

Plasmids are autonomous DNA molecules that can replicate independently and transfer horizontally between bacterial cells. They play a key role in disseminating adaptive traits, such as antimicrobial resistance and virulence. Understanding plasmid mobility and its association with these traits is crucial to microbial ecology, public health and genomic surveillance. Several databases have been developed to catalogue plasmids assembled from bacterial isolates and metagenomic samples. However, differences in database construction and curation can introduce biases that affect subsequent analyses. In this study, we compare three distinct plasmid genome datasets -- the NCBI Reference Sequence Database (RefSeq), the Integrated Microbial Genomes & Microbiomes system (IMG/PR) from bacterial isolates (I) and microbiomes (M) -- to assess the influence of data origin on inferences about plasmid mobility types, antimicrobial resistance genes (ARGs), virulence genes (VGs) and host taxonomy. Our analysis reveals that plasmids assembled from metagenomes tend to be smaller than those assembled from isolates. RefSeq plasmids are enriched in conjugative plasmids (pCONJ) and display a higher frequency of ARGs and VGs. In contrast, regardless of whether they originate from isolates or metagenomes, IMG/PR plasmids are enriched in mobilizable plasmids (pMOB). Furthermore, ARGs are more frequently associated with highly mobile plasmids, particularly pCONJ. These findings highlight the importance of database selection in studies of plasmid epidemiology, functional potential and mobility. Standardised curation practices and cross-database comparisons are essential to ensure robust and reproducible insights into plasmid-mediated gene flow. ImportancePlasmids are DNA molecules that can replicate and transfer between bacteria, thereby helping to spread genes that enable bacteria to survive and adapt in different environments. This gene exchange plays a significant part in bacterial evolution. Researchers study these processes using plasmid databases, but the way these databases are constructed can influence the conclusions that are drawn. In this study, we found that key traits, such as those involved in antibiotic resistance and the ability to cause disease, are more often linked to plasmids with greater mobility, particularly in databases containing more clinical samples. However, our results demonstrate that the choice of dataset can significantly impact our understanding of the dissemination of critical genes among bacteria. These findings are valuable for tracking and controlling antibiotic resistance and disease, and highlight the need for carefully constructed, representative databases to support accurate research into how bacteria share genes.

genomics↗

bioRxiv2021

The power of dying slowly - persistence as unintentional dormancy

Persistence is a state of bacterial dormancy where cells with low metabolic activity and growth rates are phenotypically tolerant to antibiotics and other cytotoxic substances. Given its obvious advantage to bacteria, several researchers have been looking for the genetic mechanism behind persistence. However, other authors argue that there is no such mechanism and that persistence results from inadvertent cell errors. In this case, the persistent population should decay according to a power-law with a particular exponent of -2. Studying persisters decay is, therefore, a valuable way to understand persistence. Here we simulated the fate of susceptible cells in laboratory experiments in the context of indirect resistance. Eventually, under indirect resistance, detoxifying drug-resistant cells save the persister cells that leave the dormant state and resume growth. The simulations presented here show that, by assuming a power-law decline, the exponent is close to -2, which is the expected value if persistence results from unintentional errors. Whether persisters are cells in a moribund state or, on the contrary, result from a genetic program, should impact the research of anti-persistent drugs. Author SummaryPersistence, a form of bacterial dormancy, was discovered in the early days of the antibiotic era. Thanks to dormancy, these cells often evade antibiotic therapy and the immune system. However, despite its clinical importance, this phenotypes nature is still under debate. Arguably, the prevailing view is that persistence is an evolved (selected for) bet-hedging mechanism to survive in the presence of cytotoxic agents such as antibiotics. In that case, the persister population should decay exponentially, although at a much slower pace than the non-persister population. A few authors recently advanced an alternative hypothesis: bacterial persistence results from many malfunctions and cell division errors. In this case, persistent populations should decay according to a power-law with exponent of -2, that is, according to 1/t2. Here we simulated the fate of susceptible bacterial cells in the presence of bactericidal antibiotics in the context of indirect resistance based on laboratory experiments performed earlier. By showing that the dynamics of persister cells is consistent with 1/t2, our results corroborate the hypothesis that the phenomenon of bacterial persistence is an accidental consequence of inadvertent cell problems and errors. If confirmed, this conclusion should impact the research strategies of anti-persistent drugs. O_QD"The following day, no one died. This fact, being absolutely contrary to lifes rules, provoked enormous and, in the circumstances, perfectly justifiable anxiety in peoples minds, for we have only to consider that in the entire forty volumes of universal history there is no mention, not even one exemplary case, of such a phenomenon ever having occurred..." Death with interruptions Jose Saramago (2005) Nobel Prize for Literature 1998 C_QD

microbiology↗

bioRxiv2020

Gene transmission and antibiotic usage are the key factors responsible for the positive correlation between antibiotic resistance gene diversity and virulence gene diversity in human metagenomes

1.This study aims to understand the cause of the recent observation that humans with a higher diversity of virulence genes in their metagenomes tend to be precisely those with higher diversity of antibiotic-resistance genes. We simulated the transferring of virulence and antibiotic-resistance genes in a community of interacting people where some take antibiotics. The diversities of the two genes types became positively correlated whenever the contagion probability between two people was higher than the probability of losing resistant genes. However, no such positive correlations arise if no one takes antibiotics. This finding holds even under changes of several simulations parameters, such as the relative or total diversity of virulence and resistance genes, the contagion probability between individuals, the loss rate of resistance genes, or the social network type. Because the loss rate of resistance genes may be shallow, we conclude that the contagion between people and antibiotic usage is the leading cause of establishing the positive correlation mentioned above. Therefore, antibiotic use and something as prosaic as the contagion between people may facilitate the emergence of virulent and multi-resistant bacteria in peoples metagenomes with a high diversity of both gene types. These superbugs may then circulate in the community.

microbiology↗