**7. Future prospects for antibiotic enhancers to treat** *P. aeruginosa* **infections**

Now that the syntheses of the bulgecins A, B and C have been accomplished and purified Lt enzymes of many bacteria are available with simple commercial high throughput assays such as ENZCHEK lysozyme™ (substrate is a fluorescein labelled sacculus from *Micrococcus lutei*), it should not be long before potent derivatives of bulgecins are developed through medicinal chemistry approaches. Combinations of enhancers with novel β-lactamase inhibitor/potent anti-pseudomonal β-lactams are possibilities in the future antibiotic arsenal.

## **8. Conclusions**

Antibiotic resistance in *P. aeruginosa* is on the rise in both inpatient and outpatient settings. β-lactams remain among the most successful antibiotics due to their potency, efficacy and safety. Traditionally, β-lactamase inhibitors have proved able to extend the life of these valuable antibiotics. However, through a variety of resistance mechanisms, *P. aeruginosa* has eluded these approaches. Lts are novel cell wall enzymes that work in concert with PBPs to facilitate numerous cellular functions (insertion of secretion systems, cell division, etc.). When both Lts and PBPs are inhibited, bacteria exhibit abnormal bulging of cell wall and osmotic lysis. Bulgecins are naturally occurring compounds that inhibit Lts. Together with β-lactams, Bulgecin A can lead to effective bacterial killing, even when *P. aeruginosa* are resistant to the partner β-lactam antibiotics. Bulgecins are a novel β-lactam enhancer that may prove beneficial in the treatment of infections with resistant *P. aeruginosa*.

## **Acknowledgements**

The author would like to acknowledge her affiliation and employment with the U.S. Department of Veteran Affairs.

**79**

**Author details**

Marion J. Skalweit

provided the original work is properly cited.

University School of Medicine, Cleveland, Ohio, USA

\*Address all correspondence to: msh5@case.edu

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

Louis Stokes Cleveland Veterans Affairs Medical Center and Case Western Reserve

*Bulgecins as β-Lactam Enhancers Against Multidrug Resistant (MDR) Pseudomonas aeruginosa*

The author is an employee of the U.S. Department of Veterans Affairs. The opinions expressed in this review are her own and do not reflect those of her employer.

*DOI: http://dx.doi.org/10.5772/intechopen.85151*

**Conflict of interest**

*Bulgecins as β-Lactam Enhancers Against Multidrug Resistant (MDR) Pseudomonas aeruginosa DOI: http://dx.doi.org/10.5772/intechopen.85151*
