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Research Project: Eliminating Fusarium Mycotoxin Contamination of Corn by Targeting Fungal Mechanisms and Adaptations Conferring Fitness in Corn and Toxicology and Toxinology Studies of Mycotoxins

Location: Toxicology & Mycotoxin Research

Title: Fungal lactamases: Their occurrence and function

item GAO, M - University Of Georgia
item Glenn, Anthony - Tony
item BLACUTT, ALEX - University Of Georgia
item Gold, Scott

Submitted to: Frontiers in Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/31/2017
Publication Date: 9/19/2017
Citation: Gao, M., Glenn, A.E., Blacutt, A.A., Gold, S.E. 2017. Fungal lactamases: Their occurrence and function. Frontiers in Microbiology. 8:1775. doi:10.3389/fmicb.2017.01775.

Interpretive Summary: Because of the way soil fungi grow and feed they are exposed to many other organisms. Antibiosis is a common means of competition between fungi and other microbes. Successful competitors must be able to counter antibiotic effects. This is frequently achieved by enzymatic degradation of antibiotics. It has long been known that bacteria protect themselves from beta-lactam antibiotics like penicillin by the action of enzymes called beta-lactamases. Beta-lactam antibiotics interfere with bacterial cell wall production. Examination of fungal genomes shows that many contain genes that look like beta-lactamases even though they are unaffected by beta-lactam antibiotics and their cell wall is completely different from bacteria. In this paper we describe the distribution lactamases in fungi with particular focus on Fusarium verticillioides, a producer of the fumonisin type mycotoxins. Fusarium species and other fungi associated with soil environments have many more of these genes than those fungi that do not encounter the soil. Evidence in F. verticillioides suggests that many of these enzymes may degrade higher order lactam compounds, and such degradation may enhance the fitness of this fungus to compete in the environment.

Technical Abstract: Fungi are absorptive feeders and thus must colonize and ramify through their substrate to survive. In so doing they are in competition, particularly in the soil, with myriad microbes. Additionally, these microbes use xenobiotic compounds as offensive weapons to compete for nutrition, and fungi must be sufficiently resistant to these xenobiotics. One prominent mechanism of xenobiotic resistance is through production of corresponding degrading enzymes. As typical examples, bacterial ß-lactamases are well known for their ability to degrade and consequently confer resistance to ß-lactam antibiotics, a serious emerging problem in health care. We have identified many fungal genes exhibiting a high degree of similarity to ß-lactamases. However, fungal cell walls are structurally unrelated to the bacterial peptidoglycan target of ß-lactams. This raises the question, why do fungi have lactamases and what are their functions? Previously, we identified and characterized one Fusarium verticillioides lactamase gene (FVEG_08291) that confers resistance to the benzoxazinoid phytoanticipins produced by maize and several other grain crop species. Since benzoxazinoids are '-lactams with five-membered rings rather than the four-membered ß-lactams, we refer to the predicted enzymes simply as lactamases, rather than ß-lactamases. An overview of fungal genomes suggests a strong positive correlation between environmental niche complexity and the number of fungal lactamase encoding genes, with soil-borne fungi showing dramatic amplification of lactamase genes compared to those fungi found in less biologically complex environments. Remarkably, Fusarium species frequently possess large numbers of (>40) lactamase genes. We hypothesize that many fungal hydrolytic lactamases are responsible for the degradation of plant or microbial xenobiotic lactam compounds. Phylogenic studies of the lactamase-encoding genes in F. verticillioides indicate most are consistent with vertical inheritance while two may have a history of horizontal gene transfer. Alignment of protein sequences revealed two conserved patterns resembling bacterial ß-lactamases, specifically those possessing PFAM domains PF00753 or PF00144. Structural predictions of F. verticillioides lactamases also suggested similar catalytic mechanisms to those of their bacterial counterparts. Overall, we present the first in-depth analysis of both “metallo-ß-lactamases” (PF00753) and “serine-based ß-lactamases” (PF00144) in fungi, and we discuss their potential relevance to fitness and resistance to antimicrobials in the environment.