New Drug Candidate SAAP-148 Shows Promise Against Drug-Resistant Bacteria

Concerns Over Drug-Resistant Bacteria

The emergence of drug-resistant bacteria has raised significant concerns regarding public health. Hospital-acquired infections are frequently linked to these resistant strains, which are capable of forming biofilms. These biofilms encase the bacteria, rendering conventional antibiotic treatments less effective. Among these bacteria are “persisters,” which can remain dormant and resistant to treatment, only to resurface later as biofilm-associated infections.

Discovering the Potential of Antimicrobial Peptides

Researchers have identified that naturally occurring antimicrobial peptides (AMPs) within the human body can pave the way for the development of new synthetic peptides, such as SAAPs, with enhanced antimicrobial and anti-biofilm properties. An article published in *Science Translational Medicine* by Dutch researchers highlighted these encouraging findings.

LL-37: A Key Human Antimicrobial Peptide

The human peptide LL-37 is a significant AMP that contributes to the immune system’s response against infections. Researchers modified the LL-37 peptide through random substitutions to create various variants. Among these, SAAP-148 emerged as the most effective. This peptide binds to bacterial membranes and causes rapid bacterial death within minutes. In vitro tests have shown that SAAP-148 effectively kills drug-resistant strains, particularly ESKAPE pathogens, which are commonly responsible for hospital-acquired infections.

SAAP-148’s Effectiveness Against Persister Bacteria

SAAP-148 demonstrated the ability to dose-dependently inhibit the formation of bacterial biofilms and eradicate existing biofilms of *Staphylococcus aureus* and *Acinetobacter baumannii*, both of which are ESKAPE pathogens. The effectiveness of SAAP-148 against persisters was also evaluated. After exposing *S. aureus* biofilms to a high dose of rifampin, a common last-resort antibiotic, the surviving persisters were treated with SAAP-148. Remarkably, no viable bacteria were detected post-treatment, indicating that SAAP-148 can eliminate persister bacteria to undetectable levels.

Topical Application and Efficacy in Wound Infections

Researchers further explored SAAP-148’s potential as a topical treatment for surface wound infections. By formulating it into an ointment, they tested its efficacy on laboratory-grown human skin and in live mouse skin infections. The results indicated that SAAP-148 was more effective in eradicating biofilm-associated wound infections compared to currently used antimicrobial ointments.

Resistance Profile of SAAP-148

In response to concerns about the development of resistance, researchers assessed the capacity of ESKAPE pathogens to develop resistance to SAAP-148 after repeated exposures. After twenty passages with SAAP-148, no resistant isolates were observed. In contrast, other antibiotics, such as rifampin and ciprofloxacin, showed significant resistance development after eight and five passages, respectively. This suggests that the rapid membrane-targeting mechanism of SAAP-148 may reduce the likelihood of developing drug-resistant bacteria.

Limitations and Future Directions

A primary limitation of the study is that SAAP-148’s efficacy was only evaluated on superficial wounds. Challenges may arise regarding the peptide’s ability to penetrate deeper tissues or the risk of degradation within the body. Future research may focus on developing tailored drug delivery systems to ensure the peptide’s survival and effective targeting.

Conclusion

The findings regarding SAAP-148 present a strong case for its advancement to clinical studies. The data suggests that SAAPs hold significant promise for the future development of novel antibiotics to combat drug-resistant bacteria.

Written by Maggie Leung, PharmD

Reference

Breij, A. D., Riool, M., Cordfunke, R. A., Malanovic, N., Boer, L. D., Koning, R. I., . . . Nibbering, P. H. (2018). The antimicrobial peptide SAAP-148 combats drug-resistant bacteria and biofilms. *Science Translational Medicine*, 10(423). doi:10.1126/scitranslmed.aan4044