As antibiotic resistance continues to be a major public health problem, antimicrobial alternatives have become critically important. Nanostructured zeolites have been considered as an ideal host for improving popular antimicrobial silver-ion-exchanged zeolites, because with very short diffusion path lengths they offer advantages in ion diffusion and release over their conventional microsized zeolite counterparts. Herein, comprehensive studies are reported on materials characteristics, silver-ion release kinetics, and antibacterial properties of silver-ion-exchanged nanostructured zeolite X with comparisons to conventional microsized silver-ion-exchanged zeolite (∼2 μm) as a reference. The nanostructured zeolites are submicrometer-sized aggregates (100-700 nm) made up of primary zeolite particles with an average primary particle size of 24 nm. The silver-ion-exchanged nanostructured zeolite released twice the concentration of silver ions at a rate approximately three times faster than the reference. The material exhibited rapid antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA) with minimum inhibitory concentration (MIC) values ranging from 4 to 16 μg/mL after 24 h exposure in various growth media and a minimum bactericidal concentration (MBC; >99.9% population reduction) of 1 μg/mL after 2 h in water. While high concentrations of silver-ion-exchanged nanostructured zeolite X were ineffective at reducing MRSA biofilm cell viability, efficacy increased at lower concentrations. In consideration of potential medical applications, cytotoxicity of the silver-ion-exchanged nanostructured zeolite X was also investigated. After 4 days of incubation, significant reduction in eukaryotic cell viability was observed only at concentrations 4-16-fold greater than the 24 h MIC, indicating low cytotoxicity of the material. Our results establish silver-ion-exchanged nanostructured zeolites as an effective antibacterial material against dangerous antibiotic-resistant bacteria.

Studies have shown that club cell secretory protein (CC16) plays important protective roles in the lungs, yet its complete biological functions are unclear. We devised a translational mouse model in order to investigate the impact of early life infections, in the context of CC16 deficiency, on lung function in adult mice. CC16 sufficient (WT) and deficient (CC16 -/- ) mice were infected with Mycoplasma pneumoniae (Mp) as weanlings and assessed as adults ( e arly l ife i nfection m odel; ELIM) and compared to adult mice infected for only three days ( a dult i nfection m odel; AIM). CC16 -/- Mp-infected mice had significantly increased airway hyperresponsiveness (AHR) in both models compared to WT mice. However, CC16 -/- mice infected in early life (ELIM) displayed significantly increased AHR compared to CC16 -/- mice infected in adulthood (AIM). In stark contrast, lung function in ELIM WT mice returned to levels similar to saline-treated controls. While WT mice cleared Mp infection in the ELIM, CC16 -/- mice remained colonized with Mp throughout the model, which likely contributed to increased airway remodeling and persistence of Muc5ac expression. When CC16 -/- mouse tracheal epithelial cells (MTECs) were infected with Mp, increased Mp colonization and collagen gene expression were also detected compared to WT cells, suggesting that CC16 plays a protective role during Mp infection, in part through epithelial-driven host defense mechanisms.

Pore-forming and hemolytic toxins are bacterial cytotoxic proteins required for virulence in many pathogens, including staphylococci and streptococci, and are notably associated with clinical manifestations of disease. Inspired by adsorption properties of naturally occurring aluminosilicates, we engineered inexpensive, laboratory-synthesized, aluminosilicate geopolymers with controllable pore and surface characteristics to remove pathogenic or cytotoxic material from the surrounding environment. In this study, macroporous and mesoporous geopolymers were produced with and without stearic acid surface modifications. Geopolymer binding efficacies were assessed by measuring adsorption of methicillin-resistant Staphylococcus aureus (MRSA) culture filtrate proteins, α-hemolysin and streptolysin-O toxins, MRSA whole cells, and antibiotics. Macroporous and mesoporous geopolymers were strong non-selective adsorbents for bacterial protein, protein toxins, and bacteria. Although some geopolymers adsorbed antibiotics, these synthesized geopolymers could potentially be used in non-selective adsorptive applications and optimized for adsorption of specific biomolecules.

The rise in antibiotic resistance in bacteria has spawned new technological approaches for identifying novel antimicrobials with narrow specificity. Current antibiotic treatment regimens and antituberculosis drugs are not effective in treating Mycobacterium abscessus . Meanwhile, antimicrobial peptides are gaining prominence as alternative antimicrobials due to their specificity toward anionic bacterial membranes, rapid action, and limited development of resistance. To rapidly identify antimicrobial peptide candidates, our group has developed a high-density peptide microarray consisting of 125,000 random synthetic peptides screened for interaction with the mycobacterial cell surface of M. abscessus morphotypes. From the array screening, peptides positive for interaction were synthesized and their antimicrobial activity was validated. Overall, six peptides inhibited the M. abscessus smooth morphotype (IC 50 = 1.7 μM for all peptides) and had reduced activity against the M. abscessus rough morphotype (IC 50 range: 13–82 μM). Peptides ASU2056 and ASU2060 had minimum inhibitory concentration values of 32 and 8 μM, respectively, against the M. abscessus smooth morphotype. Additionally, ASU2060 (8 μM) was active against Escherichia coli , including multidrug-resistant E. coli clinical isolates, Pseudomonas aeruginosa , and methicillin-resistant Staphylococcus aureus . ASU2056 and ASU2060 exhibited no significant hemolytic activity at biologically relevant concentrations, further supporting these peptides as promising therapeutic candidates. Moreover, ASU2060 retained antibacterial activity after preincubation in human serum for 24 h. With antimicrobial resistance on the rise, methods such as those presented here will streamline the peptide discovery process for targeted antimicrobial peptides.

Club Cell Secretory Protein (CC16) plays many protective roles within the lung; however, the complete biological functions, especially regarding the pulmonary epithelium during infection, remain undefined. We have previously shown that CC16-deficient (CC16−/−) mouse tracheal epithelial cells (MTECs) have enhanced Mp burden compared to CC16-sufficient (WT) MTECs; therefore, in this study, we wanted to further define how the pulmonary epithelium responds to infection in the context of CC16 deficiency. Using mass spectrometry and quantitative proteomics to analyze proteins secreted apically from MTECs grown at an air–liquid interface, we investigated the protective effects that CC16 elicits within the pulmonary epithelium during Mycoplasma pneumoniae (Mp) infection. When challenged with Mp, WT MTECs have an overall reduction in apical protein secretion, whereas CC16−/− MTECs have increased apical protein secretion compared to their unchallenged controls. Following Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) assessment, many of the proteins upregulated from CC16−/− MTECS (unchallenged and during Mp infection) were related to airway remodeling, which were not observed by WT MTECs. These findings suggest that CC16 may be important in providing protection within the pulmonary epithelium during respiratory infection with Mp, which is the major causative agent of community-acquired pneumoniae.