Continuous production of lactic acid from molasses by free and immobilized Sporolactobacillus cellulosolvens

Both free and immobilized cells of Sporolactobacillus cellulosolvens, in continuous culture on molasses (50 g sugar 1^-1) at 40°C, had maximum lactic acid productivities of 0.03 and 0.06 mol l^-1 h, at dilution rates of 0.27 and 0.25 h^-1, respectively.S.S. Kanwar is with the Department of Biotechnology, Guru Nanak Dev University, Amritsar-143 005, India; B.S. Chadha is with the Department of Microbiology, Guru Nanak Dev University, Amritsar-143 005, India. H.K. Tewari and V.K. Sharma are with the Department of Microbiology, Punjab Agricultural University, Ludhiana-141 004, India.     

Repurposing phytochemicals as anti-virulent agents to attenuate quorum sensing-regulated virulence factors and biofilm formation in Pseudomonas aeruginosa

Unregulated consumption and overexploitation of antibiotics have paved the way for emergence of antibiotic-resistant strains and ‘superbugs’. Pseudomonas aeruginosa is among the opportunistic nosocomial pathogens causing devastating infections in clinical set-ups globally. Its artillery equipped with diversified virulence elements, extensive antibiotic resistance and biofilms has made it a ‘hard-to-treat’ pathogen. The pathogenicity of P. aeruginosa is modulated by an intricate cell density-dependent mechanism called quorum sensing (QS). The virulence artillery of P. aeruginosa is firmly controlled by QS genes, and their expression drives the aggressiveness of the infection. Attempts to identify and develop novel antimicrobials have seen a sharp rise in the past decade. Among different proposed mechanisms, a novel anti-virulence approach to target pseudomonal infections by virtue of anti-QS and anti-biofilm drugs appears to occupy the centre stage. In this respect, bioactive phytochemicals have gained prominence among the scientific community owing to their significant quorum quenching (QQ) properties. Recent studies have shed light on the QQ activities of various phytochemicals and other drugs in perturbing the QS-dependent virulence in P. aeruginosa. This review highlights the recent evidences that reinforce the application of plant bioactives for combating pseudomonal infections, their advantages and shortcomings in anti-virulence therapy.     

Regulated Interaction of Tegument Proteins UL16 and UL11 from Herpes Simplex Virus

It is well known that proteins in the tegument (located between the viral capsid and envelope proteins) play critical roles in the assembly and budding of herpesviruses. Tegument proteins UL16 and UL11 of herpes simplex virus (HSV) are conserved among all the Herpesviridae. Although these proteins directly interact in vitro, UL16 was found to colocalize poorly with UL11 in cotransfected cells. To explain this discrepancy, we hypothesized that UL16 is initially made in an inactive form and is artificially transformed to the binding-competent state when cells are disrupted. Consistent with a regulated interaction, UL16 was able to fully colocalize with UL11 when a large C-terminal segment of UL16 was removed, creating mutant UL16(1-155). Moreover, membrane flotation assays revealed a massive movement of this mutant to the top of sucrose gradients in the presence of UL11, whereas both the full-length UL16 and the C-terminal fragment (residues 156 to 373) remained at the bottom. Further evidence for the presence of a C-terminal regulatory domain was provided by single-amino-acid substitutions at conserved cysteines (C269S, C271S, and C357S), which enabled the efficient interaction of full-length UL16 with UL11. Lastly, the binding site for UL11 was further mapped to residues 81 to 155, and to our surprise, the 5 Cys residues within UL16(1-155) are not required, even though the modification of free cysteines in UL16 with N-ethylmaleimide does in fact prevent binding. Collectively, these results reveal a regulatory function within the C-terminal region of UL16 that controls an N-terminal UL11-binding activity.     

Biosurfactant production by Pseudomonas sp. and its role in aqueous phase partitioning and biodegradation of chlorpyrifos

Aim:  To study the effect of biosurfactant on aqueous phase solubility and biodegradation of chlorpyrifos.
Methods and Results:  A Pseudomonas sp. (ChlD), isolated from agricultural soil by enrichment culture technique in the presence of chlorpyrifos, was capable of producing biosurfactant (rhamnolipids) and degrading chlorpyrifos (0·01 g l⁻¹). The partially purified rhamnolipid biosurfactant preparation, having a CMC of 0·2 g l⁻¹, was evaluated for its ability to enhance aqueous phase partitioning and degradation of chlorpyrifos (0·01 g l⁻¹) by ChlD strain. The best degradation efficiency was observed at 0·1 g l⁻¹ supplement of biosurfactant, as validated by GC and HPLC studies.
Conclusion:  The addition of biosurfactant at 0·1 g l⁻¹ resulted in more than 98% degradation of chlorpyrifos when compared to 84% in the absence of biosurfactant after 120-h incubation.
Significance and Impact of the Study:  This first report, to the best of our knowledge, on enhanced degradation of chlorpyrifos in the presence of biosurfactant(s), would help in developing bioremediation protocols to counter accumulation of organophosphates to toxic/carcinogenic levels in environment.     

Characteristics and programme-defined treatment outcomes among childhood tuberculosis (TB) patients under the national TB programme in Delhi

Background

Childhood tuberculosis (TB) patients under India''s Revised National TB Control Programme (RNTCP) are managed using diagnostic algorithms and directly observed treatment with intermittent thrice-weekly short-course treatment regimens for 6–8 months. The assignment into pre-treatment weight bands leads to drug doses (milligram per kilogram) that are lower than current World Health Organization (WHO) guidelines for some patients.

Objectives

The main aim of our study was to describe the baseline characteristics and treatment outcomes reported under RNTCP for registered childhood (age <15 years) TB patients in Delhi. Additionally, we compared the reported programmatic treatment completion rates between children treated as per WHO recommended anti-TB drug doses with those children treated with anti-TB drug doses below that recommended in WHO guidelines.

Methods

For this cross-sectional retrospective study, we reviewed programme records of all 1089 TB patients aged <15 years registered for TB treatment from January to June, 2008 in 6 randomly selected districts of Delhi. WHO disease classification and treatment outcome definitions are used by RNTCP, and these were extracted as reported in programme records.

Results and Conclusions

Among 1074 patients with records available, 651 (61%) were females, 122 (11%) were <5 years of age, 1000 (93%) were new cases, and 680 (63%) had extra-pulmonary TB (EP-TB)—most commonly peripheral lymph node disease [310 (46%)]. Among 394 pulmonary TB (PTB) cases, 165 (42%) were sputum smear-positive. The overall reported treatment completion rate was 95%. Similar reported treatment completion rates were found in all subgroups assessed, including those patients whose drug dosages were lower than that currently recommended by WHO. Further studies are needed to assess the reasons for the low proportion of under-5 years of age TB case notifications, address challenges in reaching all childhood TB patients by RNTCP, the accuracy of diagnosis, and the clinical validity of reported programme defined treatment completion.     

Transformation of some hydroxy amino acids to other amino acids.

It has been observed that beta-hydroxy-alpha-amino acids are transformed into other amino acids, when heated in dilute solutions with phosphorous acid, phosphoric acid or their ammonium salts. It has been shown that as in the case of previously reported glycine-aldehyde reactions, glycine also reacts with acetone to give beta-hydroxyvaline under prebiologically feasible conditions. It is suggested, therefore, that the formation of beta-hydroxy-alpha-amino acids and their transformation to other amino acids may have been a pathway for the synthesis of amino acids under primitive earth conditions.     

Pseudomonas cepacia lipase--mediated transesterification reactions of hydrocinnamates

Use of lipase from Pseudomonas cepacia in transesterifcation reactions of ethyl hydrocinnamate with different alcohols has been examined. Among the alcohols tested, viz., n-butanol, iso-amyl alcohol, benzyl alcohol, n-octanol and 1-phenylethanol, only n-butanol yielded the transesterified product. Among the solvents tested, viz., n-heptane, n-hexane, cyclohexane, toluene, diisopropylether and n-butanol, the initial rate of transesterification proceeded in the order cyclohexane > n-heptane > n-hexane > diisopropylether > n-butanol > toluene. Using hexane as the solvent and a substrate to enzyme ratio of 1:5, the substrate to alcohol ratio was varied to maximize the yield. n-Butyl hydrocinnamate was obtained in 92% yield in 48 hr by employing a 1:1 (wt/wt) ratio of ethyl hydrocinnamate to lipase and a 1:5 (vol/vol) ratio of ethyl hydrocinnamate to n-butanol in hexane.     

Super sural neurofasciocutaneous flaps in acute traumatic heel reconstructions

Conventional reversed sural flaps have been used to cover heel defects; however, the experience of the authors indicates that the reach of these flaps falls just short of the critical area to be covered. With the limitation being the location of the flap (the middle third of the leg), the authors thought that if the flap territory were extended proximally, they would have a super flap with immense potential. Nevertheless, the critical question remained, "How far?" The massive earthquake in January of 2001 in Gujarat, India, made medical personnel pressed for time, manpower, resources, and other ancillary supports. The authors were forced to make some innovations in their management of extensive heel defects. On the basis of preexisting anatomic studies, they developed the possibility of using distally based neuroskin flaps of huge dimensions that extend well beyond the conventional confines. The versatility of this extended, reversed, neuro-fasciocutaneous flap in regard to its reliability and safety, despite its huge dimensions, is commendable. The hallmarks of this successful extended sural flap, which the authors used to cover large heel defects, were basically accurate understanding of the anatomy and the use of Doppler to map the perforators and the lesser saphenous vein for inclusion in the lie of the pedicle. The authors share their experience of five cases of difficult heel reconstructions salvaged with this flap, which made them attempt to define maximum flap dimensions that can be harvested. The authors learned that the flap can be extended proximally to include the entire upper one-third of the leg posteriorly, drastically improving its reach and size, without compromising safety. The largest flap used measured 17 x 16 cm, far more than ever reported in the literature. The flaps truly deserve the classification of "super," which is usually reserved for Ponten's flaps.     

1,2,3-Triazole Derivatives as an Emerging Scaffold for Antifungal Drug Development against Candida albicans: A Comprehensive Review

Candida infections are most prominent among fungal infections majorly target immunocompromised and hospitalized patients and cause significant morbidity and mortality. Candida albicans is the notorious and most prevalent among all pathogenic Candida strains. Its emerging resistance toward available antifungal agents making it hard to tackle and emerging as global healthcare emergency. Simultaneously, 1,2,3-triazole nucleus is a privileged scaffold that is gaining importance in antifungal drug development due to being a prominent bioactive linker and isostere of triazole based antifungal class core 1,2,4-triazole. Numerous reports have been updated in scientific literature in last few decades related to utilization of 1,2,3-triazole nucleus in antifungal drug development against Candida albicans. Present review will shed light on various preclinical studies focused on development of 1,2,3-triazole derivatives targeting Candida albicans along with brief highlight on clinical trials and newly approved drugs. Structure-activity relationship has been precisely discussed for each architect along with future perspective that will help medicinal chemists in design and development of potent antifungal agents for tackling infections derived from Candida albicans.