Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological Universitygrid.59025.3b, Singapore.
Department of Oral Biology, University of Florida College of Dentistry, Gainesville, Florida, USA.
J Bacteriol. 2022 Jul 19;204(7):e0061521. doi: 10.1128/jb.00615-21. Epub 2022 Jun 27.
Enterococcus faecalis is often coisolated with Pseudomonas aeruginosa in polymicrobial biofilm-associated infections of wounds and the urinary tract. As a defense strategy, the host innately restricts iron availability at infection sites. Despite their coprevalence, the polymicrobial interactions of these two species in biofilms and under iron-restricted conditions remain unexplored. Here, we show that E. faecalis inhibits P. aeruginosa growth within biofilms when iron is restricted. E. faecalis lactate dehydrogenase () gives rise to l-lactate production during fermentative growth. We find that an E. faecalis mutant fails to inhibit P. aeruginosa growth. Additionally, we demonstrate that expression is induced under iron-restricted conditions, resulting in increased lactic acid exported and, consequently, a reduction in local environmental pH. Together, our results suggest that E. faecalis synergistically inhibits P. aeruginosa growth by decreasing environmental pH and l-lactate-mediated iron chelation. Overall, this study emphasizes the importance of the microenvironment in polymicrobial interactions and how manipulating the microenvironment can impact the growth trajectory of bacterial communities. Many infections are polymicrobial and biofilm-associated in nature. Iron is essential for many metabolic processes and plays an important role in controlling infections, where the host restricts iron as a defense mechanism against invading pathogens. However, polymicrobial interactions between pathogens are underexplored under iron-restricted conditions. Here, we explore the polymicrobial interactions between commonly coisolated E. faecalis and P. aeruginosa within biofilms. We find that E. faecalis modulates the microenvironment by exporting lactic acid which further chelates already limited iron and also lowers the environmental pH to antagonize P. aeruginosa growth under iron-restricted conditions. Our findings provide insights into polymicrobial interactions between bacteria and how manipulating the microenvironment can be taken advantage of to better control infections.
粪肠球菌常与铜绿假单胞菌共同分离培养，存在于多微生物生物膜相关的伤口和尿路感染感染。作为一种防御策略，宿主在感染部位固有地限制铁的可用性。尽管它们同时存在，但这两种生物在生物膜中和铁限制条件下的多微生物相互作用仍未得到探索。在这里，我们表明，当铁受到限制时，粪肠球菌会抑制生物膜内铜绿假单胞菌的生长。粪肠球菌乳酸脱氢酶 () 在发酵生长过程中产生 l-乳酸。我们发现粪肠球菌突变体不能抑制铜绿假单胞菌的生长。此外，我们证明在铁限制条件下诱导 表达，导致更多的乳酸被排出，从而降低局部环境 pH 值。总之，我们的研究结果表明，粪肠球菌通过降低环境 pH 值和 l-乳酸介导的铁螯合作用，协同抑制铜绿假单胞菌的生长。总的来说，这项研究强调了微生物环境在多微生物相互作用中的重要性，以及如何操纵微生物环境会影响细菌群落的生长轨迹。许多感染是多微生物和生物膜相关的。铁对许多代谢过程是必不可少的，在控制感染方面起着重要作用，宿主将铁作为一种防御机制来对抗入侵的病原体。然而，在铁限制条件下，病原体之间的多微生物相互作用仍未得到充分探索。在这里，我们探索了通常共同分离的粪肠球菌和铜绿假单胞菌在生物膜内的多微生物相互作用。我们发现，粪肠球菌通过输出乳酸来调节微环境，进一步螯合已经有限的铁，并降低环境 pH 值，从而在铁限制条件下抑制铜绿假单胞菌的生长。我们的研究结果提供了关于细菌之间多微生物相互作用的见解，以及如何利用微环境来更好地控制感染。
