Phage therapy in the Covid-19 era: Advantages over antibiotics.

Today, the entire world is battling to contain the spread of COVID-19. Massive efforts are being made to find a therapeutic solution in the shortest possible time. However, the research community is becoming increasingly concerned about taking a shortsighted strategy without contemplating the long-term consequences. For example, It has been reported that only 8.4% of total COVID-19 patients develop a secondary bacterial infection. In comparison, 74.6% of them are administered with antibiotics as prophylactic treatment. We contend that overuse of broad-spectrum antibiotics increases the likelihood of AMR development and negatively affects the patient's recovery due to the prevalence of the "gut-lung axis.". Consequently, the use of antibiotics to treat COVID-19 patients must be rationalized, or an alternative treatment must be sought that does not risk contributing to AMR development and positively impacts the treatment outcomes. Phage therapy, a century-old concept, is one of the most promising approaches that can be adapted to serve this purpose. This review emphasizes the negative impact of excessive antibiotic use in COVID-19 treatment and provides an overview of how phage therapy can be used as an alternative treatment option. We have argued that targeted killing (narrow spectrum) and anti-inflammatory (which can target the primary cause of mortality in COVID-19) properties of phages can be an effective alternative to antibiotics.

Biomedical evaluation of a novel nitrogen oxides releasing wound dressing.

Chronic wounds are a major cause for both suffering and economical losses. Management of chronic non-healing wounds requires multipronged approach. They are polymicrobial and agonizing for the patient due to associated pain. Moist dressing providing antimicrobial action is a highly desirable chronic wound management option. Here we report a hydrogel based dressing that possesses the antimicrobial properties of acidified sodium nitrite and the homeostatic property of a hydrogel. The dressing was developed by combining citric acid cross-linked cotton gauze and sodium nitrite loaded gelatin. The cotton gauze was cross-linked with citric acid by pad-dry-curing in presence of nano-titania catalyst. The cotton gauze-gelatin hydrogel combination was gamma-irradiated and freeze-dried. At the time of application, the freeze-dried dressing is wetted by sodium nitrite solution. The dressing has a fluid uptake ability of 90 % (w/v) and the water vapour evaporation rate was estimated to be 2,809 ± 20 g/m(2)/day. The dressing showed significant antimicrobial activity against both planktonic and biofilm forms and was effective during consecutive re-uses. Cytotoxicity study showed inhibition of fibroblasts, but to a lesser extent than clinically administered concentrations of antiseptic like povidone iodine. Storage at 37 °C over a 3 month period resulted in no significant loss of its antimicrobial activity.

Novel biocatalytic polymer-based antimicrobial coatings as potential ureteral biomaterial: preparation and in vitro performance evaluation.

Catheters and other indwelling devices placed inside human body are prone to bacterial infection, causing serious risk to patients. Infections associated with implants are difficult to resolve, and hence the prevention of bacterial colonization of such surfaces is quite appropriate. In this context, the development of novel antimicrobial biomaterials is currently gaining momentum. We describe here the preparation and antibacterial properties of an enzyme-embedded polycaprolactone (PCL)-based coating, coimpregnated with the antibiotic gentamicin sulfate (GS). The enzyme uses PCL itself as substrate; as a result, the antibiotic gets released at a rate controlled by the degradation of the PCL base. In vitro drug release studies demonstrated sustained release of GS from the PCL film throughout its lifetime. By modulating the enzyme concentration in the PCL film, we were able to vary the lifetime of the coating from 33 h to 16 days. In the end, the polymer is completely degraded, delivering the entire load of the antibiotic. The polymer exhibited antibacterial properties against three test isolates: Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. Foley urinary catheters coated with the modified polymer exhibited sustained in vitro release of GS over a 60-h period. The results suggest that the antibiotic-plus-enzyme-loaded polymer can be used as tunable self-degrading antimicrobial biomaterial coating on catheters.

Nutrition induced pleomorphism and budding mode of reproduction in Deinococcus radiodurans.

BACKGROUND: Morphological adaptation is an important biological function of a microorganism to cope with its environment. Pleomorphism (to exist in a number of morphological forms) took centre stage in many discussions wherein a bacterium exhibits morphological transition and altered mode of reproduction in response to an environmental condition. FINDINGS: To strengthen the concept on pleomorphism in bacteria, we report here different cell morphologies of Deinococcus radiodurans in response to variation in nutrient concentration. From our studies we attempt primary evidence towards the presence of significant population of monomer cells of D. radiodurans in specific culture condition. In this report we also illustrate with scanning electron micrographs an unusual budding mode of reproduction in D. radiodurans which was not reported till date for this group of bacteria. CONCLUSION: In a holistic view the study reflects on bacterial shape (morphotypes) and the physiological adaptation to a particular nutrient environment. The discovery of budding mode of reproduction in Deinococcus will be of interest to microbiologists. It can serve as a model system to understand the mechanism of budding process at molecular level.

Formation of aerobic granules in the presence of a synthetic chelating agent.

This paper examines the development of aerobic granular sludge in the presence of a synthetic chelating agent, nitrilotriacetic acid (NTA), in sequencing batch reactors (SBR). The growth of seed sludge at 0.26 mM, 0.52 mM and 1.05 mM of NTA was found to be significantly lower as compared to that in the absence of NTA. Aerobic granulation was significantly enhanced in the three SBRs (R2, R3 and R4), which were fed with 0.26 mM, 0.52 mM and 1.05 mM of NTA as a co-substrate, in comparison to the acetate-alone fed SBR (R1). After 2 months of operation, the mean diameter of the biomass stabilized at 0.35 mm in R1 (acetate alone), as compared to 2.18 mm in R4 (1.05 mM NTA+acetate). NTA degradation was established in SBRs, with almost complete removal during the SBR cycle. Batch experiments also showed efficient degradation of NTA by the aerobic granules.

Bioaugmentation of aerobic microbial granules with Pseudomonas putida carrying TOL plasmid.

This paper describes results of a successful bioaugmentation experiment on aerobic granular sludge using Pseudomonas putida KT2442 cells bearing the TOL (pWWO) plasmid. The methodology was designed to monitor incorporation of the added donor cells into pre-existent microbial granules and the subsequent plasmid transfer to the autochthonous microbial community using shake flask microcosms. Expression of reporter proteins (GFP and DsRed) allowed in situ monitoring of donor cell attachment and plasmid transfer to the recipient cells using confocal laser scanning microscopy. Concomitant with donor integration and transconjugant proliferation in the granules, a significant increase in degradation of benzyl alcohol (used as sole substrate) was observed in the augmented microcosms. In contrast, control microcosms (with non-augmented granules) did not show any noticeable increase in the degradation of the substrate. This study shows that bioaugmentation of aerobic granular sludge via donor colonization and plasmid transfer is feasible for enhanced biodegradation.

Dynamics of Deinococcus radiodurans under controlled growth conditions.

Deinococcus radiodurans is a potent radiation resistant bacterium with immense potential in nuclear waste treatment. In this investigation, the translational and rotational dynamics of dilute suspensions of D. radiodurans cultured under controlled growth conditions was studied by the polarized and depolarized dynamic light-scattering (DLS) techniques. Additionally, confocal laser scanning microscopy was used for characterizing the cultured samples and also for identification of D. radiodurans dimer, tetramer, and multimer morphologies. The data obtained showed translational diffusion coefficients (DT) of 1.2 x 10(-9), 1.97 x 10(-9), and 2.12 x 10(-9) cm2 /s, corresponding to an average size of 3.61, 2.22, and 2.06 microm, respectively, for live multimer, tetramer, and dimer forms of D. radiodurans. Depolarized DLS experiments showed very slow rotational diffusion coefficients (DR) of 0.182/s for dimer and 0.098/s for tetramer morphologies. No measurable rotational diffusion was observed for multimer form. Polarized DLS measurements on live D. radiodurans confirmed that the bacterium is nonmotile in nature. The dynamics of the dead dimer and tetramer D. radiodurans were also studied using polarized and depolarized DLS experiments and compared with the dynamics of live species. The dead cells were slightly smaller in size when compared to the live cells. However, no additional information could be obtained for dead cells from the polarized and depolarized dynamic light-scattering studies.