The DmsABC S-oxide reductase is an essential component of a novel, hypochlorite-inducible system of extracellular stress defense in .

Defenses against oxidative damage to cell components are essential for survival of bacterial pathogens during infection, and here we have uncovered that the DmsABC S-/N-oxide reductase is essential for virulence and in-host survival of the human-adapted pathogen, . In several different infection models, Δ strains showed reduced immunogenicity as well as lower levels of survival in contact with host cells. Expression of DmsABC was induced in the presence of hypochlorite and paraquat, closely linking this enzyme to defense against host-produced antimicrobials.

Bacterial acetate metabolism and its influence on human epithelia.

Short-chain fatty acids are known modulators of host-microbe interactions and can affect human health, inflammation, and outcomes of microbial infections. Acetate is the most abundant but least well-studied of these modulators, with most studies focusing on propionate and butyrate, which are considered to be more potent. In this mini-review, we summarize current knowledge of acetate as an important anti-inflammatory modulator of interactions between hosts and microorganisms.

Access to highly specialized growth substrates and production of epithelial immunomodulatory metabolites determine survival of Haemophilus influenzae in human airway epithelial cells.

Haemophilus influenzae (Hi) infections are associated with recurring acute exacerbations of chronic respiratory diseases in children and adults including otitis media, pneumonia, chronic obstructive pulmonary disease and asthma. Here, we show that persistence and recurrence of Hi infections are closely linked to Hi metabolic properties, where preferred growth substrates are aligned to the metabolome of human airway epithelial surfaces and include lactate, pentoses, and nucleosides, but not glucose that is typically used for studies of Hi growth in vitro. Enzymatic and physiological investigations revealed that utilization of lactate, the preferred Hi carbon source, required the LldD L-lactate dehydrogenase (conservation: 98.

The Alternative Sigma Factor RpoE2 Is Involved in the Stress Response to Hypochlorite and Survival of .

Extracytoplasmic function (ECF) sigma factors underpin the ability of bacteria to adapt to changing environmental conditions, a process that is particularly relevant in human pathogens that inhabit niches where human immune cells contribute to high levels of extracellular stress. Here, we have characterized the previously unstudied RpoE2 ECF sigma factor from the human respiratory pathogen (Hi) and its role in hypochlorite-induced stress. Exposure of to oxidative stress (HOCl, HO) increased gene expression, and the activity of RpoE2 was controlled by a cytoplasmic 67-aa anti-sigma factor, HrsE.

Peptide Methionine Sulfoxide Reductase from Is Required for Protection against HOCl and Affects the Host Response to Infection.

Peptide methionine sulfoxide reductases (Msrs) are enzymes that repair ROS-damage to sulfur-containing amino acids such as methionine, ensuring functional integrity of cellular proteins. Here we have shown that unlike the majority of pro- and eukaryotic Msrs, the peptide methionine sulfoxide reductase (MsrAB) from the human pathobiont (Hi) is required for the repair of hypochlorite damage to cell envelope proteins, but more importantly, we were able to demonstrate that MsrAB plays a role in modulating the host immune response to Hi infection. Loss of MsrAB resulted in >1000-fold increase in sensitivity of Hi to HOCl-mediated killing, and also reduced biofilm formation and in-biofilm survival.

Glucose Catabolism Leading to Production of the Immunometabolite Acetate Has a Key Contribution to the Host Airway-Pathogen Interplay.

Chronic obstructive pulmonary disease (COPD) is characterized by abnormal inflammatory responses and impaired airway immunity, which provides an opportunistic platform for nontypeable (NTHi) infection. Clinical evidence supports that the COPD airways present increased concentrations of glucose, which may facilitate proliferation of pathogenic bacteria able to use glucose as a carbon source. NTHi metabolizes glucose through respiration-assisted fermentation, leading to the excretion of acetate, formate, and succinate.

Metabolic analyses reveal common adaptations in two invasive Haemophilus influenzae strains.

Non-typeable Haemophilus influenzae (NTHi) is a major pathogen in upper and lower respiratory tract infections in humans, and is increasingly also associated with invasive disease. We have examined two unrelated NTHi invasive disease isolates, R2866 and C188, in order to identify metabolic and physiological properties that distinguish them from respiratory tract disease isolates such as Hi2019. While the general use of the Hi metabolic network was similar across all three strains, the two invasive isolates secreted increased amounts of succinate, which can have anti-inflammatory properties.

Health Care System Measures to Advance Preconception Wellness: Consensus Recommendations of the Clinical Workgroup of the National Preconception Health and Health Care Initiative.

Preconception wellness reflects a woman's overall health before conception as a strategy to affect health outcomes for the woman, the fetus, and the infant. Preconception wellness is challenging to measure because it attempts to capture health status before a pregnancy, which may be affected by many different service points within a health care system. The Clinical Workgroup of the National Preconception Health and Health Care Initiative proposes nine core measures that can be assessed at initiation of prenatal care to index a woman's preconception wellness.