Branching Out: Alterations in Bacterial Physiology and Virulence Due to Branched-Chain Amino Acid Deprivation

Abstract

The branched-chain amino acids (BCAAs [Ile, Leu, and Val]) represent important nutrients in bacterial physiology, with roles that range from supporting protein synthesis to signaling and fine-tuning the adaptation to amino acid starvation. In some pathogenic bacteria, the adaptation to amino acid starvation includes induction of virulence gene expression: thus, BCAAs support not only proliferation during infection, but also the evasion of host defenses.

Transcriptional profiling of threePseudomonas syringaepv.actinidiaebiovars reveals different responses to apoplast-like conditions related to strain virulence

“…The induction of anmK, encoding an anhydro-1,6-muramic acid kinase involved in cell wall metabolism, may contribute to the virulence of Psa3 given its similar role in Pto(57).In Psa2, we observed the induction of genes related to branched-chain amino acid metabolism, including those required for the synthesis of core metabolic precursors such as pyruvate, acetyl-CoA and oxaloacetate. Branched-chain amino acids are important nutrients but also act as signals that induce virulence gene expression, which in some Gram-negative bacteria is regulated via the leucineresponsive regulatory protein Lrp(58,59). The Psa2 lrp gene was not modulated by minimal medium, suggesting that branched-chain amino acids regulate virulence via other pathways, as shown for Xanthomonas oryzae pv.…”

Through the Looking Glass: Chiral Recognition of Substrates and Products at the Active Sites of Racemases and Epimerases

“…[75] IleE preferentially catalyzest he epimerization of l-Ile and d-allo-Ile with Lys280 and Asp222 acting as the enantiospecific Brønsted base catalysts that abstract the C2-proton from l-Ile and d-allo-Ile, respectively (Scheme 2); [74] however, the enzymea lso catalyzest he racemizationo re pimerization of norvaline, norleucine, Val, 2-aminobutanoic acid, Leu, Phe, Met, and l-allo-Ile, but with varying levels of reduced specific activity. [72] Indeed, IleE participates in the production of branchedchain d-amino acids in lactic acid bacteria, and it has become evident over the past decadet hat these d-amino acids play important regulatory roles in bacteria, [76,77] including remodeling of the cell wall in Vibrio cholera, [78] and biofilm disassembly in Bacilluss ubtilis. [79] Consequently,e nzymes catalyzing the biosynthesis of branched-chain d-amino acids are attractive targets for the development of antimicrobialagents.…”

The branched chain aminotransferase IlvE promotes growth, stress resistance and pathogenesis ofListeria monocytogenes

“…To optimize membrane fluidity in different environments, Gram-positive bacteria alter the ratio of ai-BCFAs to iso-BCFAs, where ai-BCFAs contribute to higher fluidity due to positioning of the terminal methyl groups on the acyl chains (18). Because BCFA synthesis depends on the acquisition and/or biosynthesis of branched chain amino acids (BCAAs: Isoleucine, Leucine and Valine [Ile, Leu, Val]) (7, 19), membrane remodeling and BCAA metabolism are tightly linked. While Lm is fully capable of synthesizing BCAAs de novo , exogenous BCAAs are required for optimal growth due in part to high demand for BCFAs in the membrane and the activity of a ribosome-mediated attenuator that limits BCAA synthesis (20, 21).…”

“…Additionally, the transcriptional regulator CodY, which senses BCAA and GTP levels, plays a major role in coordinating BCAA metabolism with virulence gene expression (21, 25–28). Importantly, when Ile levels are high, CodY inhibits de novo BCAA synthesis, and when Ile levels are low, this inhibition is relieved, allowing the bacteria to synthesize vital BCAAs (7). Thus, the ability of Lm to sense and regulate BCAA levels, particularly Ile, and to implement BCFA remodeling is an important attribute for adaptation to changing environments, especially in stress conditions as found in the mammalian host.…”