Research has shed important new light on the enemies-turned-allies that allow\u00a0bacteria\u00a0to\u00a0exchange genes, including those linked to antimicrobial resistance\u00a0(AMR).\u00a0<\/p>\n
The\u00a0insights,\u00a0which\u00a0expand our understanding of\u00a0the major\u00a0global\u00a0health threat of\u00a0AMR,\u00a0came as John\u00a0Innes Centre researchers\u00a0investigated the\u00a0curious phenomena of gene transfer agents (GTAs).\u00a0<\/p>\n
These\u00a0gene-carrying\u00a0particles look like\u00a0bacteriophages (viruses\u00a0that infect bacteria), but\u00a0they\u00a0have been\u00a0domesticated\u00a0from ancient viruses\u00a0and put to beneficial use under\u00a0the\u00a0control of the bacterial\u00a0host\u00a0cell.\u00a0<\/p>\n
Acting as\u00a0couriers,\u00a0they take up parcels\u00a0of host\u00a0bacterial\u00a0DNA and\u00a0deliver\u00a0them\u00a0to\u00a0neighbouring\u00a0bacteria. This\u00a0“selfless”\u00a0sharing,\u00a0known as horizontal gene\u00a0transfer,\u00a0can rapidly spread useful traits\u00a0including genes that confer resistance to antibiotic drugs used to treat infections.\u00a0<\/p>\n
A crucial\u00a0GTA\u00a0life stage\u00a0is\u00a0host\u00a0cell lysis:\u00a0the breaking down of a\u00a0host\u00a0cell\u00a0to release\u00a0DNA-packed GTA particles.\u00a0Previously,\u00a0it was\u00a0unclear\u00a0how GTA particles escape their host bacterial cells.\u00a0<\/p>\n
In this study,\u00a0which appears in\u00a0Nature Microbiology,\u00a0the team used a\u00a0deep sequencing-based\u00a0screening method to\u00a0identify\u00a0genes critical for GTA function in the model bacterium\u00a0Caulobacter\u00a0crescentus.\u00a0<\/p>\n
This\u00a0identified\u00a0a three-gene\u00a0control\u00a0hub,\u00a0LypABC,\u00a0encoding\u00a0bacterial proteins. When\u00a0these\u00a0lypABC\u00a0genes were\u00a0deleted,\u00a0bacteria could no longer lyse to release\u00a0GTA particles. In contrast,\u00a0by overexpressing the\u00a0lypABC\u00a0hub they obtained\u00a0a very high\u00a0proportion of lysing cells.\u00a0Together,\u00a0these experiments\u00a0identified\u00a0LypABC\u00a0as\u00a0a\u00a0control mechanism\u00a0for GTA-mediated cell lysis.\u00a0<\/p>\n
Surprisingly,\u00a0LypABC\u00a0resembles a bacterial\u00a0anti-phage\u00a0immune system\u00a0since it\u00a0contains\u00a0protein domains which are typically\u00a0required\u00a0for\u00a0defence\u00a0against viruses.\u00a0However,\u00a0this\u00a0collaborative effort between\u00a0the John Innes Centre, the University of York, and the Rowland Institute at Harvard,\u00a0suggests\u00a0it has been repurposed\u00a0to release GTA particles\u00a0for gene transfer.\u00a0<\/p>\n
They also\u00a0identified\u00a0a regulatory protein which is\u00a0required\u00a0for strict control of both GTA activation and GTA-mediated lysis.\u00a0This control is important as\u00a0misregulation\u00a0of\u00a0LypABC\u00a0is highly toxic to bacterial cells.\u00a0<\/p>\n
In highlighting the plasticity of bacterial domains, the study\u00a0advances fundamental knowledge of how gene transfer occurs between bacterial cells and\u00a0offers an important clue to understanding how\u00a0AMR\u00a0occurs.\u00a0<\/p>\n
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What’s\u00a0particularly interesting is that\u00a0LypABC\u00a0looks like an immune system, yet bacteria are using it to release GTA particles. It suggests that immune systems can be repurposed to help bacteria share DNA with each other\u00a0–\u00a0a process that can contribute to the spread of antibiotic resistance<\/a>.”<\/p>\n
Dr. Emma Banks, Royal Commission for the Exhibition of 1851 Research Fellow,\u00a0John Innes Centre\u00a0<\/p>\n
<\/p>\n The next\u00a0step\u00a0for the research is to discover\u00a0how\u00a0the\u00a0LypABC\u00a0control hub\u00a0is activated and how it functions\u00a0to control the rupture of bacterial cells and release of GTA particles.\u00a0<\/p>\n “A bacterial CARD-NLR-like immune system controls the release of gene transfer agents”,\u00a0appears in\u00a0Nature Microbiology.\u00a0<\/p>\n Source:<\/p>\n Journal reference:<\/p>\n
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