Targeted anticancer pre-vinylsulfone covalent inhibitors of carbonic anhydrase IX.

We designed novel pre-drug compounds that transform into an active form that covalently modifies particular His residue in the active site, a difficult task to achieve, and applied to carbonic anhydrase (CAIX), a transmembrane protein, highly overexpressed in hypoxic solid tumors, important for cancer cell survival and proliferation because it acidifies tumor microenvironment helping invasion and metastases processes. The designed compounds have several functionalities: (1) primary sulfonamide group recognizing carbonic anhydrases (CA), (2) high-affinity moieties specifically recognizing CAIX among all CA isozymes, and (3) forming a covalent bond with the His64 residue. Such targeted covalent compounds possess both high initial affinity and selectivity for the disease target protein followed by complete irreversible inactivation of the protein via covalent modification.

CspZ variant-specific interaction with factor H incorporates a metal site to support Lyme borreliae complement evasion.

Polymorphic microbial immune evasion proteins dictate the pathogen species- or strain-specific virulence. Metals can impact how microbial proteins confer host-pathogen interactions, but whether this activity can be allelically variable is unclear. Here, we investigate the polymorphic CspZ protein of Lyme disease spirochete bacteria to assess the role of metals in protein-protein interaction.

Recombinant design of the enzymatically active domain of phage Enc34 endolysin to improve its activity against Gram-negative bacteria.

Endolysins are bacteriophage-encoded peptidoglycan-degrading enzymes with potential applications for treating multidrug-resistant bacterial infections. While exogenously applied endolysins are active against Gram-positive bacteria in their native form, Gram-negative bacteria are protected from such activity of most native endolysins by an outer membrane. However, it was shown that recombinant endolysins can be designed to efficiently lyse Gram-negative bacteria from without as well.

Isolation and Characterization of a Novel Jumbo Phage HPP-Temi Infecting Pa9 and Increasing Host Sensitivity to Ciprofloxacin.

is a bacteria responsible for many hospital-acquired infections. Phages are promising alternatives for treating infections, which are often intrinsically resistant. The combination of phage and antibiotics in clearing bacterial infection holds promise due to increasing reports of enhanced effectiveness when both are used together.

Isolation and Characterization of a Novel -Infecting Bacteriophage, JELG-KS1.

Representatives of the bacterial genus are some of the most notorious aquaculture pathogens associated with a range of diseases in different fish species. As the world forges toward the post-antibiotic era, alternative options for combating bacterial pathogens are needed. One such alternative option is phage biocontrol.