In vitro antibacterial and anti-biofilm activities of antimicrobial cationic peptides (AMPs) - melittin and colistin - both alone and in combination with antibiotics were evaluated against clinical isolates of Gram-negative bacteria. Minimum inhibitory concentration (MIC) and fractional inhibitory concentration (FIC) index were determined by the microbroth dilution and chequerboard techniques, respectively. The time-kill curve (TKC) method was used for determining the bactericidal activities of AMPs alone and in combination. Measurements of anti-biofilm activities were performed spectrophotometrically for both inhibition of attachment and 24-hour biofilm formation at MIC or subMIC. According to MIC90 values, the most active agents against Pseudomonas aeruginosa, Escherichia coli and Klebsiella pneumoniae were colistin, imipenem and ciprofloxacin, respectively. In combination studies, synergistic effects were mostly seen with colistin-imipenem against E. coli and K. pneumoniae (50 and 54%, respectively), colistin-ciprofloxacin against P. aeruginosa (77%). In TKC studies, synergism was observed with almost all expected combinations, even more frequently than chequerboard method. All of the antimicrobial agents were able to inhibit attachment and 24-hour biofilm formation between 0-57% at 1/10 × MIC and 7-73% at 1 × or 1/10 × MIC, respectively. AMPs seem to be a good candidate for antimicrobial chemotherapy with their antibacterial and anti-biofilm activities as a single agent or in combination with antibiotics.
Crimean-Congo Hemorrhagic Fever Virus (CCHFV) causes a life-threatening disease with up to a 40% mortality rate. With no approved medical countermeasures, CCHFV is considered a public health priority agent. The non-neutralizing mouse monoclonal antibody (mAb) 13G8 targets CCHFV glycoprotein GP38 and protects mice from lethal CCHFV challenge when administered prophylactically or therapeutically. Here, we reveal the structures of GP38 bound with a human chimeric 13G8 mAb and a newly isolated CC5-17 mAb from a human survivor. These mAbs bind overlapping epitopes with a shifted angle. The broad-spectrum potential of c13G8 and CC5-17 and the practicality of using them against Aigai virus, a closely related nairovirus were examined. Binding studies demonstrate that the presence of non-conserved amino acids in Aigai virus corresponding region prevent CCHFV mAbs from binding Aigai virus GP38. This information, coupled with in vivo efficacy, paves the way for future mAb therapeutics effective against a wide swath of CCHFV strains.
The recent pandemic of COVID-19 has caused a tremendous alarm around the world. Details of the infection process in the host have significant bearings on both recovery from the disease and on the correlates of the protection from the future exposures. One of these factors is the presence and titers of neutralizing Abs (NAbs) in infected people. In the current study, we set out to investigate NAbs in the recovered subjects discharged from the hospital in full health. Serum samples from a total of 49 documented consecutive COVID-19 subjects were included in the study. All the subjects were adults, and serum samples collected during the discharge were tested in viral neutralization, enzyme immunoassay (EIA), and Western immunoblot tests against viral Ags. Even though a majority of the recovered subjects had raised significant NAb titers, there is a substantial number of recovered patients (10 out of 49) with no or low titers of NAbs against the virus. In these cohorts as well as in patients with high NAb titers, viral Ag binding Abs were detectable in EIA tests. Both NAb titers and EIA detectable Abs are increased in patients experiencing a severe form of the disease, and in older patients the Ab titers were heightened. The main conclusion is that the recovery from SARS-CoV-2 infection is not solely dependent on high NAb titers in affected subjects, and this recovery process is probably produced by a complex interplay between many factors, including immune response, age of the subjects, and viral pathology.
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