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1. Amphiphilic polymer therapeutics: an alternative platform in the fight against antibiotic resistant bacteria

   https://doi.org/10.1039/D0BM01865A  

   Takahashi, Haruko; Caputo, Gregory A.; Kuroda, Kenichi (April 2021, Biomaterials Science)

   null (Ed.)

   As we are on the cusp of the “post-antibiotic” era due to rapid spread of drug resistant bacteria, there is an urgent need for new antimicrobials that are not susceptible to bacterial resistance mechanisms. In this review, we will discuss the recent development of “polymer therapeutics” with antimicrobial activity. Learning from host-defence peptides, we propose the biomimetic design of synthetic polymers to target bacterial cell membranes, which act by compromising the membrane integrity. The discussion is extended to the future challenges and opportunities of antimicrobial polymers for clinical applications. 

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2. Exploring Titanium(IV) Complexes as Potential Antimicrobial Compounds

   https://doi.org/10.3390/antibiotics11020158  

   Rodríguez, Israel; Fernández-Vega, Lauren; Maser-Figueroa, Andrea N.; Sang, Branlee; González-Pagán, Patricia; Tinoco, Arthur D. (February 2022, Antibiotics)

   Due to the rapid mutation of pathogenic microorganisms, drug-resistant superbugs have evolved. Antimicrobial-resistant germs may share their resistance genes with other germs, making them untreatable. The search for more combative antibiotic compounds has led researchers to explore metal-based strategies centered on perturbing the bioavailability of essential metals in microbes and examining the therapeutic potential of metal complexes. Given the limited knowledge on the application of titanium(IV), in this work, eight Ti(IV) complexes and some of their corresponding ligands were screened by the Community for Open Antimicrobial Drug Discovery for antimicrobial activity. The compounds were selected for evaluation because of their low cytotoxic/antiproliferative behavior against a human non-cancer cell line. At pH 7.4, these compounds vary in terms of their solution stability and ligand exchange lability; therefore, an assessment of their solution behavior provides some insight regarding the importance of the identity of the metal compound to the antimicrobial therapeutic potential. Only one compound, Ti(deferasirox)2, exhibited promising inhibitory activity against the Gram-positive bacteria methicillin-resistant Staphylococcus aureus and minimal toxicity against human cells. The ability of this compound to undergo transmetalation with labile Fe(III) sources and, as a consequence, inhibit Fe bioavailability and ribonucleotide reductase is evaluated as a possible mechanism for its antibiotic effect. 

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3. Bioprospecting saline gradient of a Wildlife Sanctuary for bacterial diversity and antimicrobial activities

   https://doi.org/DOI 10.1186/s13104-017-2711-9  

   DeLuca, Mara; King, Riley; Morsy, Mustafa (January 2017, BMC research notes)

   Antibiotic-resistant bacteria are becoming a global crisis, causing death of thousands of people and significant economic impact. The discovery of novel antibiotics is crucial to saving lives and reducing healthcare costs. To address the antibiotic-resistant crisis, in collaboration the Small World Initiative, which aims to crowdsource novel antibiotic discovery, this study aimed to identify antimicrobial producing bacteria and bacterial diversity in the soil of the Stimpson Wildlife Sanctuary, an inland area with a soil salt gradient. 

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4. Horizontal Gene Transfer Is the Main Driver of Antimicrobial Resistance in Broiler Chicks Infected with Salmonella enterica Serovar Heidelberg

   https://doi.org/10.1128/mSystems.00729-21  

   Oladeinde, Adelumola; Abdo, Zaid; Press, Maximilian O.; Cook, Kimberly; Cox, Nelson A.; Zwirzitz, Benjamin; Woyda, Reed; Lakin, Steven M.; Thomas, Jesse C.; Looft, Torey; et al (August 2021, mSystems)

   Garrido, Daniel (Ed.)

   ABSTRACT The overuse and misuse of antibiotics in clinical settings and in food production have been linked to the increased prevalence and spread of antimicrobial resistance (AR). Consequently, public health and consumer concerns have resulted in a remarkable reduction in antibiotics used for food animal production. However, there are no data on the effectiveness of antibiotic removal in reducing AR shared through horizontal gene transfer (HGT). In this study, we used neonatal broiler chicks and Salmonella enterica serovar Heidelberg, a model food pathogen, to test if chicks raised antibiotic free harbor transferable AR. We challenged chicks with an antibiotic-susceptible S . Heidelberg strain using various routes of inoculation and determined if S . Heidelberg isolates recovered carried plasmids conferring AR. We used antimicrobial susceptibility testing and whole-genome sequencing (WGS) to show that chicks grown without antibiotics harbored an antimicrobial resistant S . Heidelberg population at 14 days after challenge and chicks challenged orally acquired AR at a higher rate than chicks inoculated via the cloaca. Using 16S rRNA gene sequencing, we found that S . Heidelberg infection perturbed the microbiota of broiler chicks, and we used metagenomics and WGS to confirm that a commensal Escherichia coli population was the main reservoir of an IncI1 plasmid acquired by S . Heidelberg. The carriage of this IncI1 plasmid posed no fitness cost to S . Heidelberg but increased its fitness when exposed to acidic pH in vitro . These results suggest that HGT of plasmids carrying AR shaped the evolution of S . Heidelberg and that antibiotic use reduction alone is insufficient to limit antibiotic resistance transfer from commensal bacteria to Salmonella enterica . IMPORTANCE The reported increase in antibiotic-resistant bacteria in humans has resulted in a major shift away from antibiotic use in food animal production. This shift has been driven by the assumption that removing antibiotics will select for antibiotic susceptible bacterial taxa, which in turn will allow the currently available antibiotic arsenal to be more effective. This change in practice has highlighted new questions that need to be answered to assess the effectiveness of antibiotic removal in reducing the spread of antibiotic resistance bacteria. This research demonstrates that antibiotic-susceptible Salmonella enterica serovar Heidelberg strains can acquire multidrug resistance from commensal bacteria present in the gut of neonatal broiler chicks, even in the absence of antibiotic selection. We demonstrate that exposure to acidic pH drove the horizontal transfer of antimicrobial resistance plasmids and suggest that simply removing antibiotics from food animal production might not be sufficient to limit the spread of antimicrobial resistance. 

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5. Needle-injectable microcomposite cryogel scaffolds with antimicrobial properties

   https://doi.org/10.1038/s41598-020-75196-1  

   Joshi Navare, Kasturi; Colombani, Thibault; Rezaeeyazdi, Mahboobeh; Bassous, Nicole; Rana, Devyesh; Webster, Thomas; Memic, Adnan; Bencherif, Sidi A. (December 2020, Scientific Reports)

   null (Ed.)

   Abstract Porous three-dimensional hydrogel scaffolds have an exquisite ability to promote tissue repair. However, because of their high water content and invasive nature during surgical implantation, hydrogels are at an increased risk of bacterial infection. Recently, we have developed elastic biomimetic cryogels, an advanced type of polymeric hydrogel, that are syringe-deliverable through hypodermic needles. These needle-injectable cryogels have unique properties, including large and interconnected pores, mechanical robustness, and shape-memory. Like hydrogels, cryogels are also susceptible to colonization by microbial pathogens. To that end, our minimally invasive cryogels have been engineered to address this challenge. Specifically, we hybridized the cryogels with calcium peroxide microparticles to controllably produce bactericidal hydrogen peroxide. Our novel microcomposite cryogels exhibit antimicrobial properties and inhibit antibiotic-resistant bacteria (MRSA and Pseudomonas aeruginosa ), the most common cause of biomaterial implant failure in modern medicine. Moreover, the cryogels showed negligible cytotoxicity toward murine fibroblasts and prevented activation of primary bone marrow-derived dendritic cells ex vivo. Finally, in vivo data suggested tissue integration, biodegradation, and minimal host inflammatory responses when the antimicrobial cryogels, even when purposely contaminated with bacteria, were subcutaneously injected in mice. Collectively, these needle-injectable microcomposite cryogels show great promise for biomedical applications, especially in tissue engineering and regenerative medicine. 

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