Diagnosing antibiotic-resistant bacterial infections
Bacterial resistance has become a serious global issue of clinical treatment. In 2013, the Centers for Disease Control and Prevention of the United States (CDC) highlighted antibiotic resistance as an urgent threat. An estimate of 2 million people infected by antibiotic‐resistant bacteria was reported. Because antibiotic resistance occurs as a natural evolution process, accurate and immediate identification of resistant bacterial strains becomes essential to prevent them from spreading. One classic example is the evolution of β‐lactamases. β‐lactamases hydrolyze β‐lactam antibiotics (e.g. penicillin), inactivating their ability. Although scientists have modified the structure of β‐lactam antibiotics to minimize the hydrolysis caused by β‐lactamases, these enzymes can evolve quickly through gene mutation and re‐gain the activity against the drugs. [1]
D-amino acid-base probes, such as FDAAs, enable quantification of bacterial peptidoglycan (the cell wall) synthesis activity. Their labeling ability is sensitive to the inhibition ability of anti-peptidoglycan compounds. Therefore, FDAA labeling can be used to investigate antibiotic effectiveness against different bacterial strains (or mutations). This could be done by co-incubating bacterial cells with FDAA and anti-peptidoglycan antibiotic for 10-50% doubling time, followed by the quantification of FDAA intensity. In non-resistance strains, the antibiotic should effectively impede peptidoglycan growth and thus give reduced FDAA intensity compared to non-treated samples. On the other hand, in resistance strains, the antibiotic may have reduced or null effect on peptidoglycan synthesis. In this case, no significant reduction of FDAA intensity could be detected.
References
[1] Shaikh et al. Antibiotic resistance and extended spectrum beta‐lactamases: Types, epidemiology and treatment. Saudi J. Biol. Sci. 2015, 22 (1), 90–101