Infectious diseases are one of the main causes of death all over the world, with antimicrobial resistance presenting a great challenge. New antibiotics need to be developed to provide therapeutic treatment options, requiring novel drug targets to be identified and pursued. DNA topoisomerases control the topology of DNA via DNA cleavage–rejoining coupled to DNA strand passage. The change in DNA topological features must be controlled in vital processes including DNA replication, transcription, and DNA repair. Type IIA topoisomerases are well established targets for antibiotics. In this review, type IA topoisomerases in bacteria are discussed as potential targets for new antibiotics. In certain bacterial pathogens, topoisomerase I is the only type IA topoisomerase present, which makes it a valuable antibiotic target. This review will summarize recent attempts that have been made to identify inhibitors of bacterial topoisomerase I as potential leads for antibiotics and use of these inhibitors as molecular probes in cellular studies. Crystal structures of inhibitor–enzyme complexes and more in-depth knowledge of their mechanisms of actions will help to establish the structure–activity relationship of potential drug leads and develop potent and selective therapeutics that can aid in combating the drug resistant bacterial infections that threaten public health.

Microorganisms associated with medicinal plants are of great interest as they are the producers of important bioactive compounds effective against common and drug-resistant pathogens. The characterization and biodiversity of fungal endophytes of the Petiveria alliacea plant and their antimicrobial production potential are of great interest as they are known for their antimicrobial and anticancer properties. In this study, we investigated the endophytic fungal microbiome associated with P. alliacea, and the endophytic fungal isolates were classified into 30 morphotypes based on their cultural and morphological characteristics. Ethyl acetate extract of fungal endophytes was obtained by liquid–liquid partitioning of culture broth followed by evaporation. The crude extract dissolved in dimethyl sulfoxide was screened for antimicrobial activity against three bacterial strains (Escherichia coli ATTC 25902, Staphylococcus aureus ATTC 14775, Bacillus subtilis NRRL 5109) and two fungal strains (Candida albicans ATTC 10231 and Aspergillus fumigatus NRRL 5109). Among the crude extracts from endophytes isolated from leaves, 65% of them showed antimicrobial activity against the bacteria tested. Similarly, 71 and 88% of the fungal crude extracts from endophytes isolated from root and stem, respectively, showed inhibitory activities against at least one of the bacterial strains tested. Crude extracts (at a concentration of 10 mg/mL) from ten of the fungal isolates have shown a zone of inhibition of more than 12 mm against both Gram-positive and negative bacteria tested. Sequenced data from isolates showing strong inhibitory activity revealed that Fusarium solani, F. proliferatum, and Fusarium oxysporium are the major endophytes responsible for bioactive potential. These results indicate that Petiveria alliacea harbors fungal endophytes capable of producing antimicrobial metabolites. Future studies need to focus on testing against drug-resistant bacteria (ESKAPE group) and other pathogenic bacteria and fungi.