No abstract

Within the repertoire of antibiotics available to a prescribing clinician, the majority affect a broad range of microorganisms, including the normal flora. The ecological disruption resulting from antibiotic treatment frequently results in secondary infections or other negative clinical consequences. To address this problem, our laboratory has recently developed a new class of pathogen-selective molecules, called specifically (or selectively) targeted antimicrobial peptides (STAMPs), based on the fusion of a species-specific targeting peptide domain with a wide-spectrum antimicrobial peptide domain. In the current study, we focused on achieving targeted killing of Streptococcus mutans, a cavity-causing bacterium that resides in a multispecies microbial community (dental plaque). In particular, we explored the possibility of utilizing a pheromone produced by S. mutans, namely, the competence stimulating peptide (CSP), as a STAMP targeting domain to mediate S. mutans-specific delivery of an antimicrobial peptide domain. We discovered that STAMPs constructed with peptides derived from CSP were potent against S. mutans grown in liquid or biofilm states but did not affect other oral streptococci tested. Further studies showed that an 8-amino-acid region within the CSP sequence is sufficient for targeted delivery of the antimicrobial peptide domain to S. mutans. The STAMPs presented here are capable of eliminating S. mutans from multispecies biofilms without affecting closely related noncariogenic oral streptococci, indicating the potential of these molecules to be developed into "probiotic" antibiotics which could selectively eliminate pathogens while preserving the protective benefits of a healthy normal flora.

Influenza A viruses (IAVs) cause seasonal pandemics and epidemics with high morbidity and mortality, which calls for effective anti-IAV agents. The glycoprotein hemagglutinin of influenza virus plays a crucial role in the initial stage of virus infection, making it a potential target for anti-influenza therapeutics development. Here we found that quercetin inhibited influenza infection with a wide spectrum of strains, including A/Puerto Rico/8/34 (H1N1), A/FM-1/47/1 (H1N1), and A/Aichi/2/68 (H3N2) with half maximal inhibitory concentration (IC50) of 7.756 ± 1.097, 6.225 ± 0.467, and 2.738 ± 1.931 μg/mL, respectively. Mechanism studies identified that quercetin showed interaction with the HA2 subunit. Moreover, quercetin could inhibit the entry of the H5N1 virus using the pseudovirus-based drug screening system. This study indicates that quercetin showing inhibitory activity in the early stage of influenza infection provides a future therapeutic option to develop effective, safe and affordable natural products for the treatment and prophylaxis of IAV infections.

The nucleotide sequence of the infectious spleen and kidney necrosis virus (ISKNV) genome was determined and found to comprise 111,362 bp with a G+C content of 54.78%. It contained 124 potential open reading frames (ORFs) with coding capacities ranging from 40 to 1208 amino acids. The analysis of the amino acid sequences deduced from the individual ORFs revealed that 35 of the 124 potential gene products of ISKNV show significant homology to functionally characterized proteins of other species. Some of the putative gene products of ISKNV showed significant homologies to proteins in the GenBank/EMBL/DDBJ databases including enzymes and structural proteins involved in virus replication, transcription, protein modification, and virus-host interaction. In addition, one major repeated sequence showing significant homology to the Red Sea bream iridovirus (RSIV) genome was identified. Based on the information obtained from biological properties (including histopathology, tissue tropisms, natural host range, and geographic distribution), physiochemical and physical properties, and genome analysis, we suggest that ISKNV, RSIV, sea bass iridovirus, grouper iridovirus, and African lampeye iridovirus may belong to a new genus of the Iridoviridae family and are tentatively referred to as cell hypertrophy iridoviruses.