Correction: A facile, one-pot reductive alkylation of aromatic and heteroaromatic amines in aqueous micellar media: a chemoenzymatic approach.

Correction for 'A facile, one-pot reductive alkylation of aromatic and heteroaromatic amines in aqueous micellar media: a chemoenzymatic approach' by Krithika Ganesh et al., Org. Biomol. Chem., 2023, 21, 4264-4268, https://doi.org/10.1039/D3OB00386H.

Correction: An efficient metal free synthesis of 2-aminobenzothiozoles - a greener approach.

Correction for 'An efficient metal free synthesis of 2-aminobenzothiozoles - a greener approach' by Krithika Ganesh et al., Org. Biomol. Chem., 2023, 21, 564-568, https://doi.org/10.1039/D2OB01981G.

Lutein: A potential antibiofilm and antiquorum sensing molecule from green microalga Chlorella pyrenoidosa.

The increasing resistance of Pseudomonas aeruginosa towards antimicrobial agents has been a major cause for the escalation of untreatable diabetic foot ulcer cases around the globe. This demands research towards alternative natural products that inhibit biofilm formation by P. aeruginosa. The study focuses on enhancing as well as understanding the anti-biofilm property of lutein from Chlorella pyrenoidosa against MTCC strain of P. aeruginosa PAO1. C. pyrenoidosa was subjected to nutrient starvation (N-, S- and P-) and their growth, biomass, chlorophyll pigments and total carotenoids were estimated. Lutein extracted from nutrient starved C. pyrenoidosa were quantified using High Performance Liquid Chromatography (HPLC) and also used for quantification of biofilm formation, cell surface hydrophobicity (CSH), extracellular polymeric substances (EPS) and pyocyanin degradation. The results showed 20 µg/mL concentration of lutein showed maximum inhibition and degradation of biofilm formation, pyocyanin production, Cell Surface Hydrophobicity Extracellular Polymeric Substances, when compared to other concentrations. Azithromycin was used as a standard drug to compare the efficiency of lutein as a potential antibiofilm compound. Docking studies confirmed the interaction of lutein with the four proteins - LasI, LasR, RhlI and RhlR, involved in the quorum sensing mechanism during biofilm formation. Among them, RhlI protein was found to strongly interact and LasI exhibiting the least interaction with lutein. Gene expression analyses of las and rhl genes in P. aeruginosa PAO1 revealed a significant down regulation of both the genes in the cultures treated with different concentrations of lutein. Therefore, it can be understood that lutein is an effective antibiofilm agent and can be used in combination with generic drugs that are used for treating diseases such as diabetic foot ulcers, which are ineffective due to high biofilm forming capability of P. aeruginosa and other bacterial species.

Novel quinoline-piperazine hybrids: the design, synthesis and evaluation of antibacterial and antituberculosis properties.

A communicable disease such as tuberculosis (TB), which takes ∼10 million lives worldwide every year, is one of the major concerns for future generations. The intake of multiple antibiotics is increasing because of the emergence of multiple drug-resistant TB (MDR-TB) to pathogens which do not respond to the first-line TB drugs. Even though numerous drugs are available on the market, there is a huge need for MDR-TB drugs. Herein, our emphasis was to synthesise a series of 2,4,6-substituted quinoline conjugated piperazine coupled sulfonamides, as well as amides, and to study and evaluate their in vitro antibacterial activity against both susceptible and resistant pathogens of Gram-positive and Gram-negative bacteria. Furthermore, their antituberculosis activity was assessed against non-virulent, virulent and MDR pathogens. Few compounds displayed inhibitory activity against bacterial growth, but two compounds displayed significant inhibitory activity against all the TB strains (lowest MIC of 10g is 0.07 µM and 11e is 1.1 µM), which are more effective than other 1st line and 2nd line TB drugs. These two compounds are less cytotoxic, and could be developed as antibiotics or MDR-TB drugs by improving their hydrophilicity.

A Review of Immunomodulatory Reprogramming by Probiotics in Combating Chronic and Acute Diabetic Foot Ulcers (DFUs).

Diabetic foot ulcers (DFUs) are characterized by a lack of angiogenesis and distal limb diabetic neuropathy. This makes it possible for opportunistic pathogens to protect the biofilm-encased micro-communities, causing a delay in wound healing. The acute and chronic phases of DFU-associated infections are distinguished by the differential expression of innate proinflammatory cytokines and tumor necrosis factors (TNF-α and -ß). Efforts are being made to reduce the microbial bioburden of wounds by using therapies such as debridement, hyperbaric oxygen therapy, shock wave therapy, and empirical antibiotic treatment. However, the constant evolution of pathogens limits the effectiveness of these therapies. In the wound-healing process, continuous homeostasis and remodeling processes by commensal microbes undoubtedly provide a protective barrier against diverse pathogens. Among commensal microbes, probiotics are beneficial microbes that should be administered orally or topically to regulate gut-skin interaction and to activate inflammation and proinflammatory cytokine production. The goal of this review is to bridge the gap between the role of probiotics in managing the innate immune response and the function of proinflammatory mediators in diabetic wound healing. We also highlight probiotic encapsulation or nanoformulations with prebiotics and extracellular vesicles (EVs) as innovative ways to tackle target DFUs.

Unusual Hypermucoviscous Clinical Isolate of Klebsiella pneumoniae with No Known Determinants of Hypermucoviscosity.

Klebsiella pneumoniae can be broadly classified into classical strains that cause drug-resistant, hospital-associated infections and hypervirulent strains that cause invasive, community-acquired, drug-susceptible infections. Hypermucoviscosity in Klebsiella pneumoniae has been associated with immune evasion and hypervirulence. A string-test-positive, hypermucoviscous strain of Klebsiella pneumoniae, P34, was isolated from the cystic lesion of a patient who reported to a tertiary care hospital in Jodhpur, Rajasthan, India. Given the antibiotic-susceptible and hypermucoviscous nature of the isolate, it was suspected to belong to the hypervirulent lineage of Klebsiella pneumoniae. However, P34 did not overproduce capsular polysaccharides and also remained susceptible to the antimicrobial effects of human serum when tested alongside strains that were non-hypermucoviscous. Sequencing of the genome of P34 revealed the absence of any large virulence plasmids or integrative conjugative elements that usually carry hypermucoviscosity- and hypervirulence-associated genes. P34 also lacked key virulence determinants such as aerobactin, yersiniabactin, and salmochelin biosynthesis clusters. In addition, P34 lacked homologs for genes associated with enhanced capsule synthesis and hypermucoviscosity, such as rmpA, rmpA2, rmpC, and rmpD (regulator of mucoid phenotype). These observations suggest that P34 may harbor novel genetic determinants of hypermucoviscosity independent of the indirectly acting rmpA and the recently described rmpD. IMPORTANCE Hypermucoviscosity is a characteristic of hypervirulent Klebsiella pneumoniae strains, which are capable of causing invasive disease in community settings. This study reports phenotyping and genomic analysis of an unusual clinical isolate of Klebsiella pneumoniae, P34, which exhibits hypermucoviscosity and yet does not harbor rmp (regulator of mucoid phenotype) genes, which are known determinants of hypermucoviscosity (rmpA and rmpD). Similar clinical isolates belonging to the K. pneumoniae complex that are hypermucoviscous but do not harbor the rmp loci have been reported from India and abroad, indicating the prevalence of unknown determinants contributing to hypermucoviscosity. Therefore, strains like P34 will serve as model systems to mechanistically study potentially novel determinants of hypermucoviscosity in the K. pneumoniae complex.

Efficacy of sub-MIC level of meropenem and ciprofloxacin against extensive drug-resistant (XDR) Pseudomonas aeruginosa isolates of diabetic foot ulcer patients.

The increasing emergence of extensive drug-resistant bacteria (XDR) among chronic diabetic foot ulcer patients (DFU) possess serious threat which leads to foot amputation. The ideal measurement estimations of the presently accessible medications are getting insufficient against extensive drug-resistant strains. For quite a long-time piperacillin monotherapy, Piperacillin-tazobactam, ceftazidime, Carbapenem class of anti-toxin, ceftalozane-Tazobactam, and so on, has been the suggested therapy towards persistent instances of diabetic foot ulcer but because of the resistance mechanism of the potent pathogens the potency and usage of the antibiotic concentration regime is under the radar. Based on this hypothesis two isolates namely VIT PC 7 &VIT PC 9 were found to be resistant to all five classes of antibiotics exhibiting extensive drug resistance (XDR). The whole-genome sequence of Pseudomonas aeruginosa VIT PC 7 and VIT PC 9 data showed the presence of various RND efflux related genes and antibiotic resistance genes. The broth microdilution assay showed minimum inhibitory concentration (MIC) for ciprofloxacin and meropenem, Synergistic test was performed through checkerboard analysis and sub-MIC concentration of ciprofloxacin/meropenem was deduced using ∑ FICI, Time kills analysis was done for varying time interval to check the maximum reduction in CFU/ml of the bacterial cells, sub-MIC level of meropenem and ciprofloxacin showed inhibitory activity at lower concentration respectively. In vitro time-kill analysis showed the decrease in the number of cells, suggesting that the synergistic antimicrobial combinations are effective in decreasing the MIC level, and combinational test involving sub-MIC level of antibiotics also showed maximum reduction in biofilm forming cells, portraying the effectiveness of both the drugs. Accordingly, an expansion in the antimicrobial spectrum can be accomplished by utilizing the ideal measurements of ciprofloxacin/meropenem in persistent condition like diabetic foot ulcer, sub-MIC level of ciprofloxacin/meropenem could be a promising choice for anticipation against the ongoing drug-resistant crisis.

Repurposing of histone deacetylase inhibitors: A promising strategy to combat pulmonary fibrosis promoted by TGF-ß signalling in COVID-19 survivors.

Coronavirus disease 2019 (COVID-19) has rapidly spread around the world causing global public health emergency. In the last twenty years, we have witnessed several viral epidemics such as severe acute respiratory syndrome coronavirus (SARS-CoV), Influenza A virus subtype H1N1 and most recently Middle East respiratory syndrome coronavirus (MERS-CoV). There were tremendous efforts endeavoured globally by scientists to combat these viral diseases and now for SARS-CoV-2. Several drugs such as chloroquine, arbidol, remdesivir, favipiravir and dexamethasone are adopted for use against COVID-19 and currently clinical studies are underway to test their safety and efficacy for treating COVID-19 patients. As per World Health Organization reports, so far more than 16 million people are affected by COVID-19 with a recovery of close to 10 million and deaths at 600,000 globally. SARS-CoV-2 infection is reported to cause extensive pulmonary damages in affected people. Given the large number of recoveries, it is important to follow-up the recovered patients for apparent lung function abnormalities. In this review, we discuss our understanding about the development of long-term pulmonary abnormalities such as lung fibrosis observed in patients recovered from coronavirus infections (SARS-CoV and MERS-CoV) and probable epigenetic therapeutic strategy to prevent the development of similar pulmonary abnormalities in SARS-CoV-2 recovered patients. In this regard, we address the use of U.S. Food and Drug Administration (FDA) approved histone deacetylase (HDAC) inhibitors therapy to manage pulmonary fibrosis and their underlying molecular mechanisms in managing the pathologic processes in COVID-19 recovered patients.

Combinatorial Drug Therapy for Controlling Pseudomonas aeruginosa and Its Association With Chronic Condition of Diabetic Foot Ulcer.

Diabetic foot ulcer (DFU) is a major complication of diabetes mellitus, major observations of DFU cases have reported on amputation of foot region, and microbial bioburden during DFU is a major cause that affects healing of the wound regions. Pathogenic microbes are routinely isolated from these wound regions, especially Staphylococcus, Pseudomonas, Klebsiella, and Escherichia coli have been reported, whereas higher prevalence of Pseudomonas species during chronic condition in the deeper part of the wound, when left untreated, leads to gangrene. Multiple drug-resistant Pseudomonas strains are a new threat because of their biofilm-forming ability, making it more potent and incurable. Acyl homoserine lactones (AHL) are a group of signaling molecules that can regulate biofilm growth, and Las and Rhl operon generally work in tandem to initiate biofilm formation by Pseudomonas species. These signaling molecules also initiate virulence factors that correlates upregulation of inflammatory responses, and AHL can be a therapeutic target in order to prevent the efficacy of multiple drug-resistant strains that form biofilm and also can be an alternative solution against control of multiple drug-resistant strains.

Comparative data analsysis of two multi-drug resistant homoserine lactone and rhamnolipid producing Pseudomonas aeruginosa from diabetic foot infected patient.

Pseudomonas aeruginosa generally forms strong biofilm during chronic condition of wound. The whole mechanism of biofilm formation works in tandem with quorum sensing circuit of the organism in order to produce virulence. Here we report the draft genome sequence of two diabetic foot ulcer Pseudomonas aeruginosa isolates (VIT PC 7 and VIT PC 9) displaying homoserine lactone, rhamnolipid producing, biofilm phenotype and antibiotic resistance genes related to carbapenem, aminoglycoside, beta- lactamase and tetracycline resistance. The whole genome sequencing library was prepared according to the Oxford Nanopore's SQK-LSK108 kit protocol on Oxford Nanopore's Minion platform. The 7.1 Mb and 6.3-Mb draft genome sequence with GC content of 65.8% and 66.4% respectively provides insight into their resistance mechanism and virulence factors.