Abstract
β-Lactamase positive bacteria represent a growing threat to human health because of their resistance to commonly used antibiotics. Therefore, development of new diagnostic methods for identification of β-lactamase positive bacteria is of high importance for monitoring the spread of antibiotic-resistant bacteria. Here, we report the discovery of a new biodegradation metabolite (H2S), generated through β-lactamase-catalyzed hydrolysis of β-lactam antibiotics. This discovery directed us to develop a distinct molecular technique for monitoring bacterial antibiotic resistance. The technique is based on a highly efficient chemiluminescence probe, designed for detection of the metabolite, hydrogen sulfide, that is released upon biodegradation of β-lactam by β-lactamases. Such an assay can directly indicate if antibiotic bacterial resistance exists for a certain examined β-lactam. The assay was successfully demonstrated for five different β-lactam antibiotics and eight β-lactam resistant bacterial strains. Importantly, in a functional bacterial assay, our chemiluminescence probe was able to clearly distinguish between a β-lactam resistant bacterial strain and a sensitive one. As far as we know, there is no previous documentation for such a biodegradation pathway of β-lactam antibiotics. Bearing in mind the data obtained in this study, we propose that hydrogen sulfide should be considered as an emerging β-lactam metabolite for detection of bacterial resistance.
Highlights
To date, β-lactams remain the most widely utilized antibiotics because of their relatively high efficiency, low cost, ease of delivery and minimal side effects.[1] β-Lactamase positive bacteria represent a growing threat to human health because of their resistance to commonly used antibiotics.[2]
Hydrogen sulfide is generated by βlactamase catalyzed biodegradation of β-lactam antibiotics
Hydrogen sulfide is a metabolite, which is generated upon biodegradation of βlactam antibiotics by β-lactamases
Summary
Β-lactams remain the most widely utilized antibiotics because of their relatively high efficiency, low cost, ease of delivery and minimal side effects.[1] β-Lactamase positive bacteria represent a growing threat to human health because of their resistance to commonly used antibiotics.[2] Of particular concern are bacteria expressing extended spectrum βlactamases such as cephalosporinases or carbapenemases; some of these strains are capable of inactivating almost all known β-lactam antibiotics.[3−5] development of diagnostic tools for identification of β-lactamase positive bacteria is of high importance for monitoring the spread of antibiotic-resistant bacteria in regard to public health. About 40 years ago, while exploring the degradation of antibiotics, it has been reported that certain β-lactam cephalosporin antibiotics decompose to release hydrogen sulfide under strong alkaline hydrolysis conditions.[21,22] This observation has encouraged us to investigate whether antibiotics containing sulfur could release hydrogen sulfide upon their biodegradation by β-lactamases Detection of such released hydrogen sulfide can be harnessed to develop a new diagnostic method for detection of β-lactam antibiotic resistance in bacteria. Probe 1 was preincubated for 45 min in PBS (pH 7.4) prior to use; sulopenem with enzymes were incubated for 30 min prior to measurement
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
