Dynamic Effect of β-Lactam Antibiotic Inactivation Due to the Inter- and Intraspecies Interaction of Drug-Resistant Microbes

Abstract

The presence of β-lactamase positive microorganisms imparts a pharmacological effect on a variety of organisms that can impact drug efficacy by influencing the function or composition of bacteria. Although studies to assess dynamic intra-and interspecies communication with bacterial communities exist, the efficacy of drug treatment and quantitative assessment of multiorganism response is not well understood due to the lack of technological advances that can be used to study coculture interactions in a dynamic format. In this study, we investigate how β-lactamase positive microorganisms can neutralize the effect of β-lactam antibiotics in a dynamic format at the inter-and intraspecies level using microbial bead technology. Three interactive models for the biological compartmentalization of organisms were demonstrated to evaluate the effect of β-lactam antibiotics on coculture systems. Our model at the intraspecies level attempts to mimic the biofilm matrix more closely as a community-level feature of microorganisms, which acknowledges the impact of nondrug-resistant species in shaping the dynamic response. In particular, the results of intraspecies studies are highly supportive of the biofilm mode of bacterial growth, which can provide structural support and protect the bacteria from an assault on host or environmental factors. Our findings also indicate that βlactamase positive bacteria can neutralize the cytotoxic effect of β-lactam antibiotics at the interspecies level when cocultured with cancer cells. Results were validated using β-lactamase positive bacteria isolated from environmental niches, which can trigger phenotypical alteration of β-lactams when cocultured with other organisms. Our compartmentalization strategy acts as an independent ecosystem and provides a new avenue for multiscale studies to assess intra-and interspecies interactions.

Microbial β-Glucuronidase Hydrogel Beads Activate Chemotherapeutic Prodrug

“…For efficient function of bacteria colonies with spatial confinement, it is necessary to evaluate the physiological characteristics of microorganisms such as sustenance, survival, and protein expression in a desired setting. If the confinement space restricts bacteria survival and function, then it could result in low expression of the encoded enzymes upon confinement. , The hydrogel-shell environment has the potential to effectively contain these bacterial colonies for several days without the disintegration of the shell. The fabrication of the hydrogel shell layer is critical for the integrity of the capsule and to be effective in inhibiting bacteria leakage while the absence of the hydrogel shell could result in leakage of bacteria from the encapsulant with growth (Figure C).…”

“…In this study, we explored bacteria-based prodrug activation to evaluate enhanced therapeutic effects on 2D cancer cells and 3D spheroid models to fill the gap in knowledge. Our previous efforts have suggested a hydrogel-based compartmentalized system for dynamic interspecies coculture studies to query bidirectional intra- and interspecies alterations. − Based on the conceived system, a probiotic Lactococcus lactis strain expressing β-glucuronidase (GUS) enzyme was encapsulated in a biofilm-like hydrogel bead. This L. lactis strain is widely used as a starter bacterium capable of producing specific enzymes in food, dairy, and health sectors .…”

An expanded metabolic pathway for androgen production by host-associated bacteria

“…P. lymphophilium API-2 strain was cultured in PYG broth for 3 d in an anaerobic chamber. Encapsulation processes were followed by the reported method 54 . Briefly, bacterial cultures in the exponential phase were collected and then thoroughly mixed with 3 wt% (w/v) of sodium alginate (Sigma) solution to a final concentration of 2.5% alginate.…”