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1. Antimicrobial Resistance Profiles of Human Commensal Neisseria Species

   https://doi.org/10.3390/antibiotics10050538  

   Goytia, Maira; Thompson, Symone T.; Jordan, Skylar V.; King, Kacey A. (May 2021, Antibiotics)

   Pathogenic Neisseria gonorrhoeae causes the sexually transmitted infection gonorrhea. N. gonorrhoeae has evolved high levels of antimicrobial resistance (AR) leading to therapeutic failures even in dual-therapy treatment with azithromycin and ceftriaxone. AR mechanisms can be acquired by genetic transfer from closely related species, such as naturally competent commensal Neisseria species. At present, little is known about the antimicrobial resistance profiles of commensal Neisseria. Here, we characterized the phenotypic resistance profile of four commensal Neisseria species (N. lactamica, N. cinerea, N. mucosa, and N. elongata) against 10 commonly used antibiotics, and compared their profiles to 4 N. gonorrhoeae strains, using disk diffusion and minimal inhibitory concentration assays. Overall, we observed that 3 of the 4 commensals were more resistant to several antibiotics than pathogenic N. gonorrhoeae strains. Next, we compared publicly available protein sequences of known AR genes, including penicillin-binding-protein 2 (PBP2) from commensals and N. gonorrhoeae strains. We found mutations in PBP2 known to confer resistance in N. gonorrhoeae also present in commensal Neisseria sequences. Our results suggest that commensal Neisseria have unexplored antibiotic resistance gene pools that may be exchanged with pathogenic N. gonorrhoeae, possibly impairing drug development and clinical treatment. 

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2. Caerin 1 Antimicrobial Peptides that Inhibit HIV and Neisseria May Spare Protective Lactobacilli

   https://doi.org/10.3390/antibiotics9100661  

   Rollins-Smith, Louise A.; Smith, Patricia B.; Ledeczi, Anna M.; Rowe, Julia M.; Reinert, Laura K. (October 2020, Antibiotics)

   null (Ed.)

   Although acquired immunodeficiency syndrome (AIDS) caused by the human immunodeficiency virus (HIV) is a manageable disease for many, it is still a source of significant morbidity and economic hardship for many others. The predominant mode of transmission of HIV/AIDS is sexual intercourse, and measures to reduce transmission are needed. Previously, we showed that caerin 1 antimicrobial peptides (AMPs) originally derived from Australian amphibians inhibited in vitro transmission of HIV at relatively low concentrations and had low toxicity for T cells and an endocervical cell line. The use of AMPs as part of microbicidal formulations would expose the vaginal microbiome to these agents and cause potential harm to protective lactobacilli. Here, we tested the effects of caerin 1 peptides and their analogs on the viability of two species of common vaginal lactobacilli (Lactobacillus rhamnosus and Lactobacillus crispatus). Several candidate peptides had limited toxicity for the lactobacilli at a range of concentrations that would inhibit HIV. Three AMPs were also tested for their ability to inhibit growth of Neisseria lactamica, a close relative of the sexually transmissible Neisseria gonorrhoeae. Neisseria lactamica was significantly more sensitive to the AMPs than the lactobacilli. Thus, several candidate AMPs have the capacity to inhibit HIV and possible N. gonorrhoeae transmission at concentrations that are significantly less harmful to the resident lactobacilli. 

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3. Photodynamic treatment of Staphylococcus aureus with non-iron hemin analogs in the presence of hydrogen peroxide

   https://doi.org/10.1039/D4MD00148F  

   Sivasubramaniam, Badhu; Washer, Benjamin; Watanabe, Yuichiro; Ragheb, Kathryn; Robinson, J. Paul; Wei, Alexander (May 2024, RSC Medicinal Chemistry)

   Bacteria subjected to antiseptic or antibiotic stress often develop tolerance, a trait that can lead to permanent resistance. To determine whether photodynamic agents could be used to counter tolerance, we evaluated three non-iron hemin analogs (M-PpIX; M = Al, Ga, In) as targeted photosensitizers for antimicrobial photodynamic inactivation (aPDI) following exposure to sublethal H2O2. Al-PpIX is an active producer of ROS whereas Ga- and In-PpIX are more efficient at generating singlet oxygen. Al- and Ga-PpIX are highly potent aPDI agents against S. aureus and methicillin-resistant strains (MRSA) with antimicrobial activity (3-log reduction in colony-forming units) at nanomolar concentrations. The aPDI activities of Al- and Ga-PpIX against S. aureus were tested in the presence of 1 mM H2O2 added at different stages of growth. Bacteria exposed to H2O2 during log-phase growth were less susceptible to aPDI but bacteria treated with H2O2 in their postgrowth phase exhibited aPDI hypersensitivity, with no detectable colony growth after treatment with 15 nM Ga-PpIX. 

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4. An osteogenic magnesium alloy with improved corrosion resistance, antibacterial, and mechanical properties for orthopedic applications

   https://doi.org/10.1002/jbm.a.37476  

   Aboutalebianaraki, Nadia; Zeblisky, Peter; Sarker, M. D.; Jeyaranjan, Aadithya; Sakthivel, Tamil S.; Fu, Yifei; Lucchi, John; Baudelet, Matthieu; Seal, Sudipta; Kean, Thomas J.; et al (December 2022, Journal of Biomedical Materials Research Part A)

   Abstract The aim of this study was to develop a novel biodegradable magnesium (Mg) alloy for bone implant applications. We used scandium (Sc; 2 wt %) and strontium (Sr; 2 wt %) as alloying elements due to their high biocompatibility, antibacterial efficacy, osteogenesis, and protective effects against corrosion. In the present work, we also examined the effect of a heat treatment process on the properties of the Mg‐Sc‐Sr alloy. Alloys were manufactured using a metal casting process followed by heat treatment. The microstructure, corrosion, mechanical properties, antibacterial activity, and osteogenic activity of the alloy were assessed in vitro. The results showed that the incorporation of Sc and Sr elements controlled the corrosion, reduced the hydrogen generation, and enhanced mechanical properties. Furthermore, alloying with Sc and Sr demonstrated a significantly enhanced antibacterial activity and decreased biofilm formation compared to control Mg. Also, culturing Mg‐Sc‐Sr alloy with human bone marrow‐derived mesenchymal stromal cells showed a high degree of biocompatibility (>90% live cells) and a significant increase in osteoblastic differentiation in vitro shown by Alizarin red staining and alkaline phosphatase activity. Based on these results, the Mg‐Sc‐Sr alloy heat‐treated at 400°C displayed optimal mechanical properties, corrosion rate, antibacterial efficacy, and osteoinductivity. These characteristics make the Mg‐Sc‐Sr alloy a promising candidate for biodegradable orthopedic implants in the fixation of bone fractures such as bone plate‐screws or intramedullary nails. 

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5. Plant defensin antibacterial mode of action against Pseudomonas species

   https://doi.org/10.1186/s12866-020-01852-1  

   Sathoff, Andrew E.; Lewenza, Shawn; Samac, Deborah A. (December 2020, BMC Microbiology)

   null (Ed.)

   Abstract Background Though many plant defensins exhibit antibacterial activity, little is known about their antibacterial mode of action (MOA). Antimicrobial peptides with a characterized MOA induce the expression of multiple bacterial outer membrane modifications, which are required for resistance to these membrane-targeting peptides. Mini-Tn 5-lux mutant strains of Pseudomonas aeruginosa with Tn insertions disrupting outer membrane protective modifications were assessed for sensitivity against plant defensin peptides. These transcriptional lux reporter strains were also evaluated for lux gene expression in response to sublethal plant defensin exposure. Also, a plant pathogen, Pseudomonas syringae pv. syringae was modified through transposon mutagenesis to create mutants that are resistant to in vitro MtDef4 treatments. Results Plant defensins displayed specific and potent antibacterial activity against strains of P. aeruginosa . A defensin from Medicago truncatula , MtDef4, induced dose-dependent gene expression of the aminoarabinose modification of LPS and surface polycation spermidine production operons. The ability for MtDef4 to damage bacterial outer membranes was also verified visually through fluorescent microscopy. Another defensin from M. truncatula , MtDef5, failed to induce lux gene expression and limited outer membrane damage was detected with fluorescent microscopy. The transposon insertion site on MtDef4 resistant P. syringae pv. syringae mutants was sequenced, and modifications of ribosomal genes were identified to contribute to enhanced resistance to plant defensin treatments. Conclusions MtDef4 damages the outer membrane similar to polymyxin B, which stimulates antimicrobial peptide resistance mechanisms to plant defensins. MtDef5, appears to have a different antibacterial MOA. Additionally, the MtDef4 antibacterial mode of action may also involve inhibition of translation. 

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