Chikungunya virus (CHIKV) is a re-emerging mosquito-borne alphavirus that has recently engendered large epidemics around the world. There is no specific antiviral for treatment of patients infected with CHIKV and development of compounds with significant anti-CHIKV activity that can be further developed to a practical therapy is urgently required. Andrographolide is derived from Andrographis paniculata, a herb traditionally used to treat a number of conditions including infections. This study sought to determine the potential of andrographolide as an inhibitor of CHIKV infection. Andrographolide showed good inhibition of CHIKV infection and reduced virus production by approximately 3log₁₀ with a 50% effective concentration (EC₅₀) of 77 μM without cytotoxicity. Time-of-addition and RNA transfection studies showed that andrographolide affected CHIKV replication and the activity of andrographolide was shown to be cell type independent. This study suggests that andrographolide has the potential to be developed further as an anti-CHIKV therapeutic agent.

The mosquito transmitted Dengue virus (DENV) remains a significant public health problem in many tropical and subtropical countries. Increasing evidence has suggested that during the infection process cellular lipids play important roles at several stages of the replication cycle. This study sought to characterize the changes in lipid metabolism gene expression and investigated the role of one enzyme, fatty acid synthase, in DENV infection. Transcriptional profiles of genes associated with lipid metabolism were evaluated by real-time PCR after infection of different cell lines (HepG2 and HEK293T/17) and with different DENVs (laboratory adapted and low passage). Expression profiles of genes were evaluated by western blotting. A critical lipid metabolism protein, fatty acid synthase was down-regulated through siRNA and inhibited with orlistat and the effect on DENV infection determined by flow cytometry, plaque assay, western blotting and confocal microscopy. The results showed alterations of gene transcription and expression were seen in genes variously associated with lipogenesis, lipolysis and fatty acid β-oxidation during DENV infection. Interference of fatty acid synthase with either siRNA or orlistat had marked effects on virus production, with orlistat having an EC50 value of 10.07 μM at 24 h post infection. However, non-structural protein expression was largely unaffected. While drug treatment reduced virus titer by up to 3Log10, no significant effect on DENV non-structural protein expression was observed, suggesting that fatty acid synthase acts through an effect on virion formation.

Extended spectrum β lactamase-producing Klebsiellapneumoniae (ESBL-KP) is being reported with high morbidity and mortality rates and is considered as the highest priority for new antimicrobial strategies. To develop an alternative antimicrobial agent, phage KP1801 with broad lytic activity was isolated. The genome of phage KP1801 was double stranded DNA of 49,835 base pairs, with a GC content of 50.26%. There were 75 putative open reading frames. Phage KP1801 was classified as being in the order Caudovirales, belonging to the Siphoviridae family. About 323 proteins were detected by shotgun proteome analysis. The phage inhibited biofilm formation and reduced pre-formed biofilm in a dose dependent manner. Scanning electron microscopic studies demonstrated a membrane damage of bacterial cells treated with phage, resulting in cell death. Prophylactic and therapeutic efficacies of the phage were evaluated in Galleriamellonella. Administration of ESBL-KP infection with phage significantly improved the survival of G.mellonella. The number of intracellular bacteria in larvae showed a significant decrease compared with untreated control while the number of phage increased. These studies suggested that phage KP1801 has the potential for development as an alternative for antibiotics and biocontrol agents against ESBL-KP infection.

The emergence of carbapenem-resistant Acinetobacter baumannii (CRAB) has been increasingly reported, leading to greater challenges in treating infections. With the development of phage therapy and phage-antibiotic combinations, it is promising to improve the treatment of bacterial infections. In the present study, a novel vB_AbaP_WU2001 (vWU2001) phage-specific CRAB with a genome of 40,792 bp was isolated. Genomic analysis disclosed that it belongs to the Autographiviridae family of the order Caudovirales. Phage vWU2001 had a broad host range with a high adsorption rate, short latent period, large burst size and good stability. The phage could reduce preformed biofilms and inhibit biofilm formation. The combination of phage vWU2001 and colistin had significantly higher bacterial growth inhibition activity than that of phage, or colistin alone. The efficacy of the combined treatment was also evaluated in Galleria mellonella. Evaluation of its therapeutic potential showed that the combination of phage and colistin resulted in a significantly greater increase in G. mellonella survival and in bacterial clearance, as compared with that of phage or colistin alone, indicating that the combination was synergistic against CRAB. The results demonstrated that phage vWU2001 has the potential to be developed as an antibacterial agent.

Multidrug-resistant Acinetobacter baumannii (MDR A. baumannii) is one of the ESKAPE pathogens that restricts available treatment options. MDR A. baumannii is responsible for a dramatic increase in case numbers of a wide variety of infections, including skin and soft tissue infections (SSTIs), resulting in pyoderma, surgical debridement, and necrotizing fasciitis. To investigate an alternative medical treatment for SSTIs, a broad range lytic Acinetobacter phage, vB _AbP_ABWU2101 (phage vABWU2101), for lysing MDR A. baumannii in associated SSTIs was isolated and the biological aspects of this phage were investigated. Morphological characterization and genomic analysis revealed that phage vABWU2101 was a new species in the Friunavirus, Beijerinckvirinae, family Autographiviridae, and order Caudovirales. Antibiofilm activity of phage vABWU2101 demonstrated good activity against both preformed biofilms and biofilm formation. The combination of phage vABWU2101 and tigecycline showed synergistic antimicrobial activities against planktonic and biofilm cells. Scanning electron microscopy confirmed that the antibacterial efficacy of the combination of phage vABWU2101 and tigecycline was more effective than the phage or antibiotic alone. Hence, our findings could potentially be used to develop a therapeutic option for the treatment of SSTIs caused by MDR A. baumannii.