Augustus Pendleton’s research while affiliated with Cornell University and other places

The gut microbiome possesses numerous biochemical enzymes that biosynthesize metabolites that impact human health. Bile acids comprise a diverse collection of metabolites that have important roles in metabolism and immunity. The gut microbiota-associated enzyme that is responsible for the gateway reaction in bile acid metabolism is bile salt hydrolase (BSH), which controls the host’s overall bile acid pool. Despite the critical role of these enzymes, the ability to profile their activities and substrate preferences remains challenging due to the complexity of the gut microbiota, whose metaproteome includes an immense diversity of protein classes. Using a systems biochemistry approach employing activity-based probes, we have identified gut microbiota-associated BSHs that exhibit distinct substrate preferences, revealing that different microbes contribute to the diversity of the host bile acid pool. We envision that this chemoproteomic approach will reveal how secondary bile acid metabolism controlled by BSHs contributes to the etiology of various inflammatory diseases.

In the human pathogen Staphylococcus aureus, branched‐chain fatty acids (BCFAs) are the most abundant fatty acids in membrane phospholipids. Strains deficient for BCFAs synthesis experience auxotrophy in laboratory culture and attenuated virulence during infection. Furthermore, the membrane of S. aureus is among the main targets for antibiotic therapy. Therefore, determining the mechanisms involved in BCFAs synthesis is critical to manage S. aureus infections. Here, we report that the overexpression of SAUSA300_2542 (annotated to encode an acyl‐CoA synthetase) restores BCFAs synthesis in strains lacking the canonical biosynthetic pathway catalyzed by the branched‐chain α‐keto acid dehydrogenase (BKDH) complex. We demonstrate that the acyl‐CoA synthetase activity of MbcS activates branched‐chain carboxylic acids (BCCAs), and is required by S. aureus to utilize the isoleucine derivative 2‐methylbutyraldehyde to restore BCFAs synthesis in S. aureus. Based on the ability of some staphylococci to convert branched‐chain aldehydes into their respective BCCAs and our findings demonstrating that branched‐chain aldehydes are in fact BCFAs precursors, we propose that MbcS promotes the scavenging of exogenous BCCAs and mediates BCFA synthesis via a de novo alternative pathway.

In the human pathogen Staphylococcus aureus , branched-chain fatty acids (BCFAs) are the most abundant fatty acids in membrane phospholipids, and strains deficient for their synthesis experience BCFAs auxotrophy in laboratory culture and attenuated virulence during infection. Thus, membrane integrity is essential for S. aureus pathogenesis. Furthermore, the membrane of S. aureus is among the main targets for antibiotic therapy. Therefore, determining the mechanisms involved in BCFAs synthesis is critical to manage S. aureus infections. Here, we report that overexpression of the bona fide acyl-CoA synthetase gene mbcS (formerly SAUSA300_2542) restores BCFAs synthesis in strains lacking the canonical biosynthetic pathway catalyzed by the branched-chain a-keto acid dehydrogenase (BKDH) complex. We demonstrate that the acyl-CoA synthetase activity of MbcS activates branched-chain carboxylic acids, and is required by S. aureus to utilize the isoleucine derivative 2-methylbutyraldehyde to restore BCFAs synthesis in S. aureus . Based on the ability of some staphylococci to convert branched-chain aldehydes into their respective branched-chain carboxylic acids and our findings demonstrating that branched-chain aldehydes are in fact BCFAs precursors, we propose that MbcS promotes the scavenging of exogenous branched-chain carboxylic acids (BCCAs) and mediates branched-chain fatty acids synthesis via a de novo alternative pathway.

Two-component systems (TCSs) are an essential way that bacteria sense and respond to their environment. These systems are usually composed of a membrane-bound histidine kinase that phosphorylates a cytoplasmic response regulator.

Deep-sea scleractinian cup corals are prominent members of Southern Ocean megabenthic communities, though little is known about their life history. This study used paraffin histology and scanning electron microscopy to characterize the reproduction of the scleractinian coral Balanophyllia malouinensis (Squires, 1961) from Burdwood Bank in the Drake Passage. Samples were taken in April and May via otter trawls, Blake trawls, and dredges on three separate cruises: one on the RV Lawrence M. Gould in 2006, and two on the RV Nathaniel B. Palmer in 2008 and 2011. B. malouinensis is gonochoric with rare hermaphroditism. All four spermatocyst stages were seen simultaneously in males; similarly, most females contained oocytes at varying stages of development, though seasonality or periodicity could not be determined without a wider range of sample dates. Average fecundity was 241 ± 184 oocytes/individual (n = 38) and not correlated to cup size. Maturing larvae were found in the mesenteries and coelenteron of females, indicating B. malouinensis broods its larvae. This study was the first to characterize the reproduction of a deep-sea Balanophyllia species and adds to a small but growing body of work seeking to understand the unique benthic communities of Burdwood Bank.