Nε-Lysine Acetylation of the Histone-Like Protein HBsu Regulates the Process of Sporulation and Affects the Resistance Properties of Bacillus subtilis Spores

Bacillus subtilis produces dormant, highly resistant endospores in response to extreme environmental stresses or starvation. These spores are capable of persisting in harsh environments for many years, even decades, without essential nutrients. Part of the reason that these spores can survive such extreme conditions is because their chromosomal DNA is well protected from environmental insults. The α/β-type small acid-soluble proteins (SASPs) coat the spore chromosome, which leads to condensation and protection from such insults. The histone-like protein HBsu has been implicated in the packaging of the spore chromosome and is believed to be important in modulating SASP-mediated alterations to the DNA, including supercoiling and stiffness. Previously, we demonstrated that HBsu is acetylated at seven lysine residues, and one physiological function of acetylation is to regulate chromosomal compaction. Here, we investigate if the process of sporulation or the resistance properties of mature spores are influenced by the acetylation state of HBsu. Using our collection of point mutations that mimic the acetylated and unacetylated forms of HBsu, we first determined if acetylation affects the process of sporulation, by determining the overall sporulation frequencies. We found that specific mutations led to decreases in sporulation frequency, suggesting that acetylation of HBsu at some sites, but not all, is required to regulate the process of sporulation. Next, we determined if the spores produced from the mutant strains were more susceptible to heat, ultraviolet (UV) radiation and formaldehyde exposure. We again found that altering acetylation at specific sites led to less resistance to these stresses, suggesting that proper HBsu acetylation is important for chromosomal packaging and protection in the mature spore. Interestingly, the specific acetylation patterns were different for the sporulation process and resistance properties of spores, which is consistent with the notion that a histone-like code exists in bacteria. We propose that specific acetylation patterns of HBsu are required to ensure proper chromosomal arrangement, packaging, and protection during the process of sporulation.

Association Between Occupational Exposure to Formaldehyde and Cognitive Impairment

Objective:To our knowledge, no study has investigated the effect of exposure to formaldehyde on cognition in the general population. Our objective was to examine the association between occupational exposure to formaldehyde and cognitive impairment in middle-aged and young- old adults (≥45 years).Methods:In the French CONSTANCES cohort, cognitive function was assessed with a standardized battery of seven cognitive tests to evaluate global cognitive function, episodic verbal memory, language abilities and executive functions (e.g., Digit Symbol Substitution Test, DSST). A global cognitive score was created using principal component analysis. Cognitive impairment was assessed in reference to norms of neuropsychological battery according to age, sex and education. Lifetime exposure to formaldehyde was assessed using a French job-exposure matrix created in the framework of the Matgéné project. After performing multiple imputation, separate modified Poisson regression models were used to evaluate the association between cognitive impairment (<25th percentile) and formaldehyde exposure (exposed/never exposed), exposure duration, cumulative exposure index (CEI), and combination of CEI and time of last exposure.Results:Among 75 322 participants (median age: 57.5 years, women: 53%), 8% were exposed to formaldehyde during their professional life. These participants were at higher risk of global cognitive impairment (for global cognitive score: adjusted relative risk, aRR, 1.17, 95% confidence interval, CI: 1.11-1.23), after adjusting for confounders (age, sex, education, income, solvent exposure, Effort–Reward Imbalance, night-shift, repetitive, and noisy work). They were at higher risk of cognitive impairment for all cognitive domains explored. Longer exposure duration and high CEI were associated with cognitive impairment, with a dose-effect relationship for exposure duration. Recent exposure was associated with impairment in all cognitive domains. Time did not fully attenuate formaldehyde-associated cognitive deficits especially in highly exposed individuals (for DSST: high past exposure aRR 1.23, 95%CI: 1.11-1.36; high recent exposure: aRR 1.24, 95%CI: 1.13-1.35).Conclusion:Our findings highlight the long-term detrimental effect of formaldehyde exposure on cognitive health in a relatively young population.

Effect of formaldehyde exposure on bacterial communities in simulating indoor environments

Indoor formaldehyde (CH2O) exceeding the recommended level is a severe threat to human health. Few studies have investigated its effect on indoor surface bacterial communities, affecting habitants' health. This study used 20-L glass containers to mimic the indoor environment with bacterial inputs from human oral respiration. The behavior of bacterial communities responding to CH2O varied among the different CH2O levels. The bacterial community structure significantly changed over time in the 0.054 mg·m−3 CH2O group, which varied from the 0.1 mg·m−3 and 0.25 mg·m−3 CH2O groups. The Chao1 and Shannon index significantly increased in the 0.054 mg·m−3 CH2O group at 6 week, while they remained unchanged in the 0.25 mg·m−3 CH2O group. At 12 week, the Chao1 significantly increased in the 0.25 mg·m−3 CH2O group, while it remained unchanged in the 0.054 mg·m−3 CH2O group. Only a few Operational Taxonomic Units (OTUs) significantly correlated with the CH2O concentration. CH2O-induced OTUs mainly belong to the Proteobacteria and Firmicutes. Furthermore, bacterial communities formed at 6 or 12 weeks differed significantly among different CH2O levels. Functional analysis of bacterial communities showed that inferred genes related to chemical degradation and diseases were the highest in the 0.25 mg·m−3 CH2O group at 12 weeks. The development of nematodes fed with bacteria collected at 12 weeks was applied to evaluate the bacterial community's hazards. This showed significantly impaired growth in the 0.1 mg·m−3 and 0.25 mg·m−3 CH2O groups. These findings confirmed that CH2O concentration and exposure time could affect the indoor bacterial community and formed bacterial communities with a possibly more significant hazard to human health after long-term exposure to high CH2O levels.