Bacterial histone HBb from Bdellovibrio bacteriovorus compacts DNA by bending.

Histones are essential for genome compaction and transcription regulation in eukaryotes, where they assemble into octamers to form the nucleosome core. In contrast, archaeal histones assemble into dimers that form hypernucleosomes upon DNA binding. Although histone homologs have been identified in bacteria recently, their DNA-binding characteristics remain largely unexplored. Our study reveals that the bacterial histone HBb (Bd0055) is indispensable for the survival of Bdellovibrio bacteriovorus, suggesting critical roles in DNA organization and gene regulation. By determining crystal structures of free and DNA-bound HBb, we unveil its distinctive dimeric assembly, diverging from those of eukaryotic and archaeal histones, while also elucidating how it binds and bends DNA through interaction interfaces reminiscent of eukaryotic and archaeal histones. Building on this, by employing various biophysical and biochemical approaches, we further substantiated the ability of HBb to bind and compact DNA by bending in a sequence-independent manner. Finally, using DNA affinity purification and sequencing, we reveal that HBb binds along the entire genomic DNA of B. bacteriovorus without sequence specificity. These distinct DNA-binding properties of bacterial histones, showcasing remarkable similarities yet significant differences from their archaeal and eukaryotic counterparts, highlight the diverse roles histones play in DNA organization across all domains of life.

Histones, traditionally known for organizing and regulating DNA in eukaryotes and archaea, have recently been discovered in bacteria, opening up a new frontier in our understanding of genome organization across the domains of life. Our study investigates the largely unexplored DNA-binding properties of bacterial histones, focusing on HBb in Bdellovibrio bacteriovorus. We reveal that HBb is essential for bacterial survival and exhibits DNA-binding properties similar to archaeal and eukaryotic histones. However, unlike eukaryotic and archaeal histones, which wrap DNA, HBb bends DNA without sequence specificity. This work not only broadens our understanding of DNA organization across different life forms but also suggests that bacterial histones may have diverse roles in genome organization.

Functional characterization of prokaryotic dark matter: the road so far and what lies ahead.

Eight-hundred thousand to one trillion prokaryotic species may inhabit our planet. Yet, fewer than two-hundred thousand prokaryotic species have been described. This uncharted fraction of microbial diversity, and its undisclosed coding potential, is known as the "microbial dark matter" (MDM). Next-generation sequencing has allowed to collect a massive amount of genome sequence data, leading to unprecedented advances in the field of genomics. Still, harnessing new functional information from the genomes of uncultured prokaryotes is often limited by standard classification methods. These methods often rely on sequence similarity searches against reference genomes from cultured species. This hinders the discovery of unique genetic elements that are missing from the cultivated realm. It also contributes to the accumulation of prokaryotic gene products of unknown function among public sequence data repositories, highlighting the need for new approaches for sequencing data analysis and classification. Increasing evidence indicates that these proteins of unknown function might be a treasure trove of biotechnological potential. Here, we outline the challenges, opportunities, and the potential hidden within the functional dark matter (FDM) of prokaryotes. We also discuss the pitfalls surrounding molecular and computational approaches currently used to probe these uncharted waters, and discuss future opportunities for research and applications.

Antibiotic Resistance Gene Diversity and Virulence Gene Diversity Are Correlated in Human Gut and Environmental Microbiomes.

Human beings have used large amounts of antibiotics, not only in medical contexts but also, for example, as growth factors in agriculture and livestock, resulting in the contamination of the environment. Even when pathogenic bacteria are the targets of antibiotics, hundreds of nonpathogenic bacterial species are affected as well. Therefore, both pathogenic and nonpathogenic bacteria have gradually become resistant to antibiotics. We tested whether there is still cooccurrence of resistance and virulence determinants. We performed a comparative study of environmental and human gut metagenomes from different individuals and from distinct human populations across the world. We found a great diversity of antibiotic resistance determinants (AR diversity [ARd]) and virulence factors (VF diversity [VFd]) in metagenomes. Importantly there is a correlation between ARd and VFd, even after correcting for protein family richness. In the human gut, there are less ARd and VFd than in more diversified environments, and yet correlations between the ARd and VFd are stronger. They can vary from very high in Malawi, where antibiotic consumption is unattended, to nonexistent in the uncontacted Amerindian population. We conclude that there is cooccurrence of resistance and virulence determinants in human gut microbiomes, suggesting a possible coselective mechanism.IMPORTANCE Every year, thousands of tons of antibiotics are used, not only in human and animal health but also as growth promoters in livestock. Consequently, during the last 75 years, antibiotic-resistant bacterial strains have been selected in human and environmental microbial communities. This implies that, even when pathogenic bacteria are the targets of antibiotics, hundreds of nonpathogenic bacterial species are also affected. Here, we performed a comparative study of environmental and human gut microbial communities issuing from different individuals and from distinct human populations across the world. We found that antibiotic resistance and pathogenicity are correlated and speculate that, by selecting for resistant bacteria, we may be selecting for more virulent strains as a side effect of antimicrobial therapy.