Linear, dimeric, tetrameric, and cyclic peptides derived from lactoferricin B, containing the RRWQWR motif, were designed, synthesized, purified, and characterized using RP-HPLC chromatography and MALDI-TOF mass spectrometry. The antibacterial activity of the designed peptides against E. coli (ATCC 11775 and 25922) and their cytotoxic effect against MDA-MB-468 and MDA-MB-231 breast cancer cell lines were evaluated. Dimeric and tetrameric peptides showed higher antibacterial activity in both bacteria strains than linear peptides. The dimeric peptide (RRWQWR)2K-Ahx exhibited the highest antibacterial activity against the tested bacterial strains. Furthermore, the peptides with high antibacterial activity exhibited significant cytotoxic effect against the tested breast cancer cell lines. This cytotoxic effect was fast and dependent on the peptide concentration. The tetrameric molecule containing RRWQWR motif has an optimal cytotoxic effect at a concentration of 22 µM. The evaluated dimeric and tetrameric peptides could be considered as candidates for developing new therapeutic agents against breast cancer. Polyvalence of linear sequences could be considered as a novel and versatile strategy for obtaining molecules with high anticancer activity.

Linear, dimeric, tetrameric, and cyclic peptides derived from lactoferricin B–containing non-natural amino acids and the RWQWR motif were synthesized, purified, and characterized using RP-HPLC, MALDI-TOF mass spectrometry, and circular dichroism. The antibacterial activity of peptides against Escherichia coli ATCC 11775, Stenotrophomonas maltophilia ATCC 13636, and Salmonella enteritidis ATCC 13076 was evaluated. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined. The synthetic bovine lactoferricin exhibited antibacterial activity against E. coli ATCC 11775 and S. enteritidis ATCC 13076. The dimeric peptide (RRWQWR)2K-Ahx exhibited the highest antibacterial activity against the tested bacterial strain. The monomeric, cyclic, tetrameric, and palindromic peptides containing the RWQWR motif exhibited high and specific activity against E. coli ATCC 11775. The results suggest that short peptides derived from lactoferricin B could be considered as potential candidates for the development of antibacterial agents against infections caused by E. coli.

Although Candida spp., is a common cause of bloodstream infections and is often associated with high mortality rates, its resistance to antifungal drugs, and the molecular mechanisms involved have been poorly studied in Colombia. Here, 123 bloodstream isolates of Candida spp. were collected. MALDI-TOF MS identification and fluconazole (FLC) susceptibility patterns were assessed on all isolates. Subsequently, sequencing of ERG11, TAC1 or MRR1, and efflux pumps were performed for resistant isolates. Out of 123 clinical strains, C. albicans accounted for 37.4%, followed by C. tropicalis 26.8%, C. parapsilosis 19.5%, C. auris 8.1%, C. glabrata 4.1%, C. krusei 2.4% and C. lusitaniae 1.6%. Resistance to FLC reached 18%. Erg11 amino acid substitutions associated with FLC-resistance (Y132F, K143R or T220L) were found in 58% of 19 FLC-resistant isolates. Furthermore, novel mutations were found in all genes studied. Regarding efflux pumps, 42% of 19 FLC-resistant Candida spp strains showed significant efflux activity. Finally, six of the 19 FLC-resistant isolates neither harbored resistance-associated mutations nor showed efflux pump activity. Although C. albicans remain the most predominant species, non-C. albicans species comprise a high proportion (62.6%). Among FLC-resistant species, C. auris (70%) and C. parapsilosis (25%) displayed the highest percentages of resistance. In 68% of FLC-resistant isolates, a mechanism that could explain their phenotype was found (e.g. mutations, flux pump activity or both). We provide evidence that endemic isolates harbor amino acid substitutions related with resistance to one of the most used molecules in the hospital setting, with Y132F being the most frequently detected one.