Gao Minglu, Glenn Anthony E, Blacutt Alex A, Gold Scott E
Department of Plant Pathology, The University of Georgia, AthensGA, United States.
Toxicology and Mycotoxin Research Unit, U.S. National Poultry Research Center, United States Department of Agriculture - Agricultural Research Service, AthensGA, United States.
Front Microbiol. 2017 Sep 19;8:1775. doi: 10.3389/fmicb.2017.01775. eCollection 2017.
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. 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 β-lactamases are well known for their ability to degrade and consequently confer resistance to β-lactam antibiotics, a serious emerging problem in health care. We have identified many fungal genes that putatively encode proteins exhibiting a high degree of similarity to β-lactamases. However, fungal cell walls are structurally different from the bacterial peptidoglycan target of β-lactams. This raises the question, why do fungi have lactamases and what are their functions? Previously, we identified and characterized one lactamase encoding gene (FVEG_08291) that confers resistance to the benzoxazinoid phytoanticipins produced by maize, wheat, and rye. Since benzoxazinoids are γ-lactams with five-membered rings rather than the four-membered β-lactams, we refer to the predicted enzymes simply as lactamases, rather than β-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 encoding genes compared to those fungi found in less biologically complex environments. Remarkably, species frequently possess large (>40) numbers of these genes. We hypothesize that many fungal hydrolytic lactamases are responsible for the degradation of plant or microbial xenobiotic lactam compounds. Alignment of protein sequences revealed two conserved patterns resembling bacterial β-lactamases, specifically those possessing PFAM domains PF00753 or PF00144. Structural predictions of lactamases also suggested similar catalytic mechanisms to those of their bacterial counterparts. Overall, we present the first in-depth analysis of lactamases in fungi, and discuss their potential relevance to fitness and resistance to antimicrobials in the environment.
真菌是吸收性营养体，因此必须在其基质中定殖并分支生长才能生存。在此过程中，它们尤其在土壤中与无数微生物竞争。这些微生物利用外源性化合物作为攻击性武器来争夺营养，而真菌必须对这些外源性物质具有足够的抗性。外源性抗性的一个突出机制是通过产生相应的降解酶。作为典型例子，细菌β-内酰胺酶以其降解β-内酰胺抗生素并因此赋予抗性的能力而闻名，这是医疗保健中一个严重的新出现问题。我们已经鉴定出许多真菌基因，这些基因推测编码与β-内酰胺酶具有高度相似性的蛋白质。然而，真菌细胞壁在结构上不同于β-内酰胺类药物的细菌肽聚糖靶点。这就提出了一个问题，为什么真菌有内酰胺酶，它们的功能是什么？以前，我们鉴定并表征了一个内酰胺酶编码基因（FVEG_08291），该基因赋予对玉米、小麦和黑麦产生的苯并恶嗪类植保素的抗性。由于苯并恶嗪类是具有五元环的γ-内酰胺，而不是四元β-内酰胺，我们将预测的酶简单地称为内酰胺酶，而不是β-内酰胺酶。对真菌基因组的概述表明，环境生态位复杂性与真菌内酰胺酶编码基因数量之间存在很强的正相关，与在生物复杂性较低环境中发现的真菌相比，土壤传播真菌的内酰胺酶编码基因有显著扩增。值得注意的是，一些物种经常拥有大量（>40）这类基因。我们假设许多真菌水解内酰胺酶负责植物或微生物外源性内酰胺化合物的降解。蛋白质序列比对揭示了两种类似于细菌β-内酰胺酶的保守模式，特别是那些具有PFAM结构域PF00753或PF00144的模式。内酰胺酶的结构预测也表明其催化机制与其细菌对应物相似。总体而言，我们首次对真菌中的内酰胺酶进行了深入分析，并讨论了它们与环境适应性和抗微生物抗性的潜在相关性。
