Nat Commun: Fatty acids present in the human body promote S. aureus resistance to FASII inhibitors
October 20, 2016 Source: Bio Valley
Window._bd_share_config={ "common":{ "bdSnsKey":{ },"bdText":"","bdMini":"2","bdMiniList":false,"bdPic":"","bdStyle":" 0","bdSize":"16"},"share":{ }};with(document)0[(getElementsByTagName('head')[0]||body).appendChild(createElement('script')) .src='http://bdimg.share.baidu.com/static/api/js/share.js?v=89860593.js?cdnversion='+~(-new Date()/36e5)]; In a new study, from the French Academy of Agricultural Sciences (INRA), the French National Institute of Health and Medical Research (INSERM), the Hôpital Cochin (APHP) Hospital, the Fifth University of Paris, the Pasteur Institute and the French National Research Researchers at the center have found that naturally occurring fatty acids in the human body increase the resistance of Staphylococcus aureus to a class of antimicrobial agents that target the biosynthesis of bacterial fatty acids. Although antimicrobial drug discovery is a top priority in research, drug resistance strategies involving host fatty acids can prevent the use of fatty acid synthesis inhibitors to treat staphylococcal infections. The results of the study were published online October 5, 2016 in the journal Nature Communications , entitled "Environmental fatty acids enable emergence of infectious Staphylococcus aureus resistant to FASII-targeted antimicrobials".
Triclosan is an antibacterial agent widely used in household products (mouthwashes, toothpastes, lotions and shower gels) and in healthcare (disinfectants and surgical sutures). It is an antibacterial agent that inhibits fatty acid synthesis (Form II fatty acid synthesis, referred to as FASII). Recently, due to potential health risks and questionable benefits, Triclosan has been excluded from the list of additives it has approved for use in Category 1 products (domestic products) by the European Commission. In 2016, the US FDA has also banned its use in antibacterial soaps. However, triclosan is still in use and new FASII inhibitors are still under development as antibiotics for future use .
In 2009, researchers have confirmed that Gram-positive bacteria (Streptococcus, Enterococcus, and Staphylococcus) can grow in the presence of FASII inhibitors by using fatty acids found in human blood. However, as a major human pathogen, the ability of S. aureus to overcome FASII inhibitors remains controversial.
The researchers then focused on the growth of S. aureus in environments containing fatty acids and triclosan. They confirmed that the mutation rate of fatty acids conferring triclosan resistance increased by about 100-fold. When triclosan is absent, some drug-resistant S. aureus develop their own fatty acids in a normal way, but can overcome this FASII inhibitor by efficiently obtaining fatty acids in the environment. S. aureus strains with these properties are highly toxic, indicating that the biocost of this mutation leading to drug resistance is lower. In fact, a database search of the Staphylococcus genome revealed that this mutation is already present in some clinical isolates of S. aureus; as expected, these isolates have been shown to be triclosan-resistant. of.
Fatty acid-rich human skin and nostrils are naturally colonized by bacteria including staphylococci. When using topical products containing FASII inhibitors such as triclosan, they may be advantageous sites for the development of resistant bacteria. This study suggests that the use of FASII inhibitors or consumer products containing them to treat staphylococcal infections may promote the emergence or spread of drug-resistant staphylococci. This highlights the importance of studying the response of bacteria to antimicrobial agents under conditions of growth that mimic natural colonization or infecting environments when developing new FASII inhibitors .
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