Staten Island, New York, United States, October 21, 2026
Acurx Pharmaceuticals, Inc. has announced the publication of preclinical research in the American Society for Microbiology’s Microbiology Spectrum journal, highlighting the potential of its DNA polymerase IIIC (Pol IIIC) inhibitor antibiotic pipeline to combat bacterial infections while preserving beneficial gut microorganisms. The study, titled The effects of novel oral preclinical PolC inhibitor antibiotic candidates on the gut microbiome in a murine thigh infection model, evaluated investigational compounds in a mouse model of methicillin-resistant Staphylococcus aureus (MRSA) infection. The findings showed that all three tested Pol IIIC inhibitor candidates reduced MRSA burden at the evaluated doses and maintained greater gut microbial diversity and metabolic function than linezolid, the comparator antibiotic. The research addresses an important challenge in antibiotic development: eliminating harmful bacteria without unnecessarily disrupting the gut microbiome, which supports digestion, metabolic activity, and protection against certain infections. Acurx’s approach targets bacterial DNA replication through inhibition of DNA polymerase IIIC, an enzyme involved in the replication process of Gram-positive bacteria. The company believes this targeted mechanism could support the development of antibiotics with a more selective spectrum of activity. However, the findings are based on preclinical animal experiments and do not establish that the investigational compounds will preserve the human microbiome or provide clinical benefits in patients. Further studies are needed to determine their safety, efficacy, dosing, and potential role in treating serious bacterial infections.
Pol IIIC Inhibitors Demonstrate Antibacterial Activity
The research examined three investigational oral antibiotic candidates designed to inhibit bacterial DNA polymerase IIIC, also referred to as PolC. This enzyme plays a central role in bacterial DNA replication, making it a potential target for developing new antibacterial medicines. The compounds were evaluated in a neutropenic mouse thigh infection model using MRSA, a bacterial pathogen associated with difficult-to-treat infections and significant healthcare burdens. All three tested Pol IIIC inhibitors reduced MRSA bacterial burden in the experimental model, supporting continued investigation of this antibiotic class. The study also examined structural modifications intended to improve the compounds’ solubility and systemic exposure, characteristics that can influence how a drug is absorbed and distributed in the body. The findings indicated that these modifications improved exposure for the novel candidates, although further optimization may be necessary to enhance tissue-level antibacterial activity. MRSA can cause skin and soft-tissue infections, bloodstream infections, pneumonia, and other serious conditions. Antibiotic resistance makes the development of new treatment options an important research priority. By targeting a bacterial enzyme involved in DNA replication, Acurx aims to develop candidates with a distinct mechanism of action from several established antibiotic classes. Nevertheless, the mouse-model results represent an early stage of research and require further validation before clinical conclusions can be drawn.
Study Highlights Potential Gut Microbiome Preservation
An important focus of the publication was the effect of treatment on the gut microbiome, the diverse community of microorganisms that inhabit the digestive tract. Antibiotics can disrupt beneficial bacterial populations alongside disease-causing organisms, potentially affecting microbial diversity and metabolic functions. In the study, the investigational Pol IIIC inhibitors maintained a Bacteroidota-dominant gut microbial community and preserved important anaerobic metabolic pathways. In contrast, linezolid was associated with more pronounced disruption of healthy anaerobic bacterial communities and their metabolic activity. The compounds also maintained higher microbial diversity under the experimental conditions. These observations suggest a possible microbiome-sparing class effect for the investigational antibiotic candidates. Preserving the gut microbiome is particularly relevant to antibiotic development because disturbances in normal intestinal bacteria can create conditions that favor certain opportunistic pathogens. However, the microbiome response observed in mice may differ from responses in humans, and the degree of preservation may depend on the drug, dose, treatment duration, and underlying condition. The study does not yet prove that these antibiotics reduce microbiome disruption or prevent secondary infections in human patients. Additional research, including carefully designed clinical studies, will be necessary to determine whether the preclinical findings translate into meaningful patient benefits.
Advertisement
Acurx Advances Development of New Antibiotic Candidates
Acurx Pharmaceuticals is developing antibiotics intended to address serious infections caused by Gram-positive bacteria, including MRSA, vancomycin-resistant Enterococcus, and Clostridioides difficile. Its lead clinical-stage candidate, ibezapolstat, is being developed for C. difficile infection, while the Pol IIIC inhibitors discussed in the new publication remain preclinical candidates for other potential indications. The company has reported that its pipeline targets infections that represent significant public health challenges because of antimicrobial resistance and limited treatment options. Certain candidates in the preclinical program may qualify for U.S. FDA Qualified Infectious Disease Product and Fast Track-related regulatory pathways, subject to the applicable eligibility and regulatory requirements. These designations do not constitute marketing approval or establish clinical effectiveness. The latest publication provides further evidence supporting investigation of Pol IIIC inhibition as a potential strategy for developing new antibiotics with a differentiated microbiome profile. Future research will need to establish the compounds’ safety, pharmacology, dose requirements, and clinical efficacy. Acurx’s findings represent a preclinical research milestone rather than a new approved antibiotic treatment, but they contribute to ongoing efforts to develop antibacterial therapies that address resistant pathogens while limiting unnecessary disruption of beneficial microorganisms.
Source: Acurx Pharmaceuticals press release
