Genomic analysis and biodesulfurization potential of a new carbon-sulfur bond cleaving Tsukamurella sp. 3OW.

Direct combustion of sulfur-enriched liquid fuel oil causes sulfur oxide emission, which is one of the main contributors to air pollution. Biodesulfurization is a promising and eco-friendly method to desulfurize a wide range of thiophenic compounds present in fuel oil. Previously, numerous bacterial strains from genera such as Rhodococcus, Corynebacterium, Gordonia, Nocardia, Mycobacterium, Mycolicibacterium, Paenibacillus, Shewanella, Sphingomonas, Halothiobacillus, and Bacillus have been reported to be capable of desulfurizing model thiophenic compounds or fossil fuels. In the present study, we report a new desulfurizing bacterium, Tsukamurella sp. 3OW, capable of desulfurization of dibenzothiophene through the carbon-sulfur bond cleavage 4S pathway. The bacterium showed a high affinity for the hydrocarbon phase and broad substrate specificity towards various thiophenic compounds. The overall genome-related index analysis revealed that the bacterium is closely related to Tsukamurella paurometabola species. The genomic pool of strain 3OW contains 57 genes related to sulfur metabolism, including the key dszABC genes responsible for dibenzothiophene desulfurization. The DBT-adapted cells of the strain 3OW displayed significant resilience and viability in elevated concentrations of crude oil. The bacterium showed a 19 and 37% reduction in the total sulfur present in crude and diesel oil, respectively. Furthermore, FTIR analysis indicates that the oil's overall chemistry remained unaltered following biodesulfurization. This study implies that Tsukamurella paurometabola species, previously undocumented in the context of biodesulfurization, has good potential for application in the biodesulfurization of petroleum oils.

Genomic characterization and comparative genomic analysis of HS-associated Pasteurella multocida serotype B:2 strains from Pakistan.

BACKGROUND: Haemorrhagic septicaemia (HS) is a highly fatal and predominant disease in livestock, particularly cattle and buffalo in the tropical regions of the world. Pasteurella multocida (P. multocida), serotypes B:2 and E:2, are reported to be the main causes of HS wherein serotype B:2 is more common in Asian countries including Pakistan and costs heavy financial losses every year. As yet, very little molecular and genomic information related to the HS-associated serotypes of P. multocida isolated from Pakistan is available. Therefore, this study aimed to explore the characteristics of novel bovine isolates of P. multocida serotype B:2 at the genomic level and perform comparative genomic analysis of various P. multocida strains from Pakistan to better understand the genetic basis of pathogenesis and virulence. RESULTS: To understand the genomic variability and pathogenomics, we characterized three HS-associated P. multocida serotype B:2 strains isolated from the Faisalabad (PM1), Peshawar (PM2) and Okara (PM3) districts of Punjab, Pakistan. Together with the other nine publicly available Pakistani-origin P. multocida strains and a reference strain Pm70, a comparative genomic analysis was performed. The sequenced strains were characterized as serotype B and belong to ST-122. The strains contain no plasmids; however, each strain contains at least two complete prophages. The pan-genome analysis revealed a higher number of core genes indicating a close resemblance to the studied genomes and very few genes (1%) of the core genome serve as a part of virulence, disease, and defense mechanisms. We further identified that studied P. multocida B:2 strains harbor common antibiotic resistance genes, specifically PBP3 and EF-Tu. Remarkably, the distribution of virulence factors revealed that OmpH and plpE were not present in any P. multocida B:2 strains while the presence of these antigens was reported uniformly in all serotypes of P. multocida. CONCLUSION: This study's findings indicate the absence of OmpH and PlpE in the analyzed P. multocida B:2 strains, which are known surface antigens and provide protective immunity against P. multocida infection. The availability of additional genomic data on P. multocida B:2 strains from Pakistan will facilitate the development of localized therapeutic agents and rapid diagnostic tools specifically targeting HS-associated P. multocida B:2 strains.

Comparing Water Transport Properties of Janus Membranes Fabricated from Copper Mesh and Foam Using a Femtosecond Laser.

One of the important aspects of manipulating and controlling liquid transport is the design of membrane surfaces. Janus membranes with opposite wettability characteristics can be manufactured for efficient directional water transfer. In this work, two types of materials were used to fabricate membranes with an asymmetric wettability behavior: copper foam and copper mesh. One side of the membranes was treated by scanning with a femtosecond laser beam, as a result of which it was converted to a superhydrophilic state, while the untreated side remained hydrophobic. Both membranes demonstrated excellent properties of a water diode through which water droplets could easily pass from the hydrophobic side to the hydrophilic side, but not vice versa. This behavior was achieved by finding the optimal laser scanning speed. This type of Janus membrane has found applications in collecting water droplets from fog; therefore, the samples obtained were also tested in terms of harvesting micro-droplets. The Janus mesh-based structure has demonstrated a higher water collection efficiency (3.9 g/cm2 h) compared to the foam-based membrane (2.5 g/cm2 h). Since the fog-water conversion efficiency decreased over time (to 0.5 g/cm2 h in 2 weeks) due to the absorbance of organic pollutants, a coating of titanium oxide was applied to the laser-treated side of the Janus membranes. As a result, the effective function of the systems became distinctly long-lasting and was well maintained for at least 60 days. Moreover, the fabricated systems were protected from further degradation by simply placing them under sunlight for several hours. Our results prove to be useful in developing asymmetric hydrophobic-superhydrophilic membranes, which have potential applications in high-precision drop control and in harvesting water from arid environments.

Sustainability of phytoremediation: Post-harvest stratagems and economic opportunities for the produced metals contaminated biomass.

Heavy metals (HMs) are indestructible and non-biodegradable. Phytoremediation presents an opportunity to transfer HMs from environmental matrices into plants, making it easy to translocate from one place to another. The ornate features of HMs' phytoremediation are biophilia and carbon neutrality, compared to the physical and chemical remediation methods. Some recent studies related to LCA also support that phytoremediation is technically more sustainable than competing technologies. However, one major post-application challenge associated with HMs phytoremediation is properly managing HMs contaminated biomass generated. Such a yield presents the problem of reintroducing HMs into the environment due to natural decomposition and release of plant sap from the harvested biomass. The transportation of high yields can also make phytoremediation economically inviable. This review presents the design of a sustainable phytoremediation strategy using an ever-evolving life cycle assessment tool. This review also discusses possible post-phytoremediation biomass management strategies for the HMs contaminated biomass management. These strategies include composting, leachate compaction, gasification, pyrolysis, torrefaction, and metal recovery. Further, the commercial outlook for properly utilizing HMs contaminated biomass was presented.

Duodenal ulcer perforation and its consequences.

Duodenal ulcer perforation, a frequent surgical emergency, needs simple closure with indirect Graham's Omentopexy which is effective with excellent results in majority of cases despite patients' late presentation. The objective of the study was to determine the frequency of postoperative complications of perforated duodenal ulcer, conducted in the Surgery Department, Jinnah Postgraduate Medical Centre, Karachi, from March 20, 2018 to September 20, 2018. The study was a descriptive case series of 108 patients of both genders with perforated duodenal ulcer > 1 week old with ASA score I & II. Patients with trauma and comorbidities were excluded. The patients underwent laparotomy and peritoneal toilet, and after noting the site of perforation indirect Graham's Omentopexy was performed. Complications like duodenal fistula, peritonitis, and paralytic ileus, and patient's death within 10 days of surgery were noted. Age ranged from 18 to 50 years with mean age of 35.027±5.13 years, mean weight 71.120±12.77 kg, mean height 1.541 ±0.09 metres, mean BMI 29.975±4.99 kg/m2, and the mean duration of complaint was 4.194±1.30 weeks. Male predominance in 75 (69.4%) patients. Duodenal fistula was seen in 10 (9.3%) patients, peritonitis 12 (11.1%), paralytic ileus 14 (13%) and mortality was in 11 (10.2%) patients.

Highly soluble and stable 'insertion domain' of the capsid penton base protein provides complete protection against infections caused by fowl adenoviruses.

In the current study, we have evaluated the protective efficacy of the 'insertion domain' which is commonly found in the capsid penton base protein of many adenoviruses. Using the 'insertion domain' of the penton base protein of a representative fowl adenovirus, fowl adenovirus serotype 4 (FAdV-4), we find that the 'insertion domain' can readily be expressed in a soluble form in the bacterial system, and can be purified in sufficient quantities through simple chromatographic methods. We demonstrate that the 'insertion domain', when employed as a subunit vaccine candidate, provides complete protection against hydropericardium syndrome, caused by FAdV-4, in chickens. The data presented here indicate that the protein, adjuvanted with Montanide™ ISA71 VG, provides complete protection in chickens against a lethal FAdV-4 challenge after administration of two doses (100 µg of the protein per dose) two weeks apart (the first dose at the 7th day of life and a booster dose at the age of 21 days). Furthermore, the purified protein can be stored at low temperatures without any observable loss in the protein integrity up to one year, tested so far. Due to the conserved nature of the 'insertion domain' across the penton base protein of fowl adenoviruses, it is suggested that homologous insertion domains could be employed as highly stable and cost-effective subunit vaccine candidates against infections caused by respective fowl adenoviruses.

Immunological characterization of chitosan adjuvanted outer membrane proteins of Salmonella enterica serovar Typhi as multi-epitope typhoid vaccine candidate.

BACKGROUND: Outer membrane proteins (OMPs) of Gram-negative bacteria have been known as potential vaccine targets due to their antigenic properties and host specificity. Here, we focused on the exploration of the immunogenic potential and protective efficacy of total OMPs of Salmonella enterica serovar Typhi due to their multi epitope properties, adjuvanted with nanoporous chitosan particles (NPCPs). The study was designed to extrapolate an effective, low cost prophylactic approach for typhoid fever being getting uncontrolled in Pakistan due to emergence of extensively drug resistant (XDR) strains. METHODS & RESULTS: The OMPs of two S. Typhi variants (with and without Vi capsule) alone and with nanoporous chitosan particles as adjuvant were comparatively analyzed for immunogenic potential in mice. Adaptive immunity was evaluated by ELISA and relative quantification of cytokine gene expression (IL4, IL6, IL9, IL17, IL10, TNF, INF and PPIA as house keeping gene) using RT-qPCR. Statistical analysis was done using Welch's test. The protection was recorded by challenging the immunized mice with 50% ×LD50 of S. Typhi. The Vi + ve-OMPs of S. Typhi showed the most promising results by ELISA and significantly high expression of IL-6, IL-10 and IL-17 and 92.5% protective efficacy with no detectable side effects. CONCLUSION: We can conclude that the OMPs of Vi + ve S. Typhi are the most promising candidates for future typhoid vaccines because of cost effective preparation without expensive purification steps and multi-epitope properties. Chitosan adjuvant may have applications for oral protein based vaccines but found less effective in injectable preparations.

New organosulfur metallic compounds as potent drugs: synthesis, molecular modeling, spectral, antimicrobial, drug likeness and DFT analysis.

During the present investigation, two new sulfonamide-based Schiff base ligands, 4-{[(2-hydroxy-3-methoxyphenyl)methylidene]amino}-N-(1,3-thiazol-2-yl)benzene-1-sulfonamide (L1) and 4-{[1-(2-hydroxyphenyl)ethylidene]amino}-N-(1,3-thiazol-2-yl)benzene-1-sulfonamide (L2), have been synthesized and coordinated with the transition metals (V, Fe, Co, Ni, Cu and Zn). The ligands were characterized by their physical (color, melting point, yield and solubility), spectral (UV-Vis, FT-IR, LC-MS, 1H NMR and 13C NMR) and elemental data. The structures of the metal complexes (1)-(12) were evaluated through their physical (magnetic and conductance), spectral (UV-Vis, FT-IR and LC-MS) and elemental data. The molecular geometries of ligands and their selected metal complexes were optimized at their ground state energies by B3LYP level of density functional theory (DFT) utilizing 6-311+G (d, p) and LanL2DZ basis set. The first principle study has been discussed for the electronic properties, the molecular electrostatic possibilities as well as the quantum chemical identifiers. An obvious transition of intramolecular charge had been ascertained from the occupied to the unoccupied molecular orbitals. The UV-Vis analysis was performed through time-dependent density functional theory (TD-DFT) by CAM-B3LYP/6-311+G (d, p) function. The in vitro antimicrobial activity was studied against two fungal (Aspergillus niger and Aspergillus flavus) and four bacterial (Staphylococcus aureus, Klebsiela pneumoniae, Escherichia coli and Bacillus subtilis) species. The antioxidant activity was executed as antiradical DPPH scavenging activity (%), total iron reducing power (%) and total phenolic contents (mg GAE g-1). Additionally, enzyme inhibition activity was done against four enzymes (Protease, α-Amylase, Acetylcholinesterase and Butyrylcholinesterase). All the synthetic products exhibited significant bioactivity which were found to enhance upon chelation due to phenomenon of charge transfer from metal to ligand.

Myths and misconception of COVID-19 among hospital sanitary workers in Pakistan: Efficacy of a training program intervention.

OBJECTIVE: Hospital sanitary workers are among the prime source to disseminate information at a massive level, however they received least attention during the pandemic COVID-19. The study was designed to investigate the prevailing myths and misconceptions of the coronavirus pandemic among the sanitary workers of health care system. Further, a systematic training program is devised and tested to demystify the false myths with discerning truth and awareness-raising in hospital sanitary workers. METHOD: A pre-post face-to-face intervention design was opted and the intervention was conducted at five locations by the project team. The intervention consisted a 3 days training program to target myths and misconceptions of hospital sanitary workers. The study was completed in 8 months starting from August, 2019 to March, 2020. Participants were recruited from local hospitals having a specialized indoor COVID treatment facility. The sample consisted of 82 participants (n = 25, 30.09% females) with age ranging from 18 to 60 years (M ± SD = 37.41 ± 10.09). FINDINGS: The results indicated that 86.4% of the participants never heard the name of the coronavirus before the pandemic in Pakistan. A majority of the participants (> 50%) believed on a very alarming but unrealistic rate of mortality i.e., 30-60%. The pre-testing showed a high prevalence of myths in all four domains (i.e., popular treatments = 24.44, conspiracy myths = 7.93, home remedies = 16.46, and COVID-reliance = 7.82). The pre and post comparison of individual myths showed significant improvement on 24 of the 26 myths with a decline ranging from 0.18 to 1.63. Overall, the intervention significantly decreased scores on all four domains of coronavirus myths. CONCLUSION: The training intervention appeared to effectively reduce myths and misconceptions of sanitary staff workers and is advised to be included as a standard training program for sanitary workers of health care system.

Blunt abdominal trauma patients presenting to a tertiary care facility of Pakistan: A three years' experience.

Blunt abdominal trauma (BAT) refers to injuries without wounds entering the peritoneal cavity due to road traffic accidents (RTA) and falls, as a result of collision or counter collision. The objective of the present study was to determine the frequency of patients with visceral injuries in blunt abdominal trauma. This study was carried out in the Department of Surgery, including ward-3 of Jinnah Post Graduate Medical Centre, Karachi, from November 2017 till November 2020. The study design was descriptive case series. During the study period, the data of 112 patients was collected, which comprised of 102 males and 10 females. All the patients between 12 to 65 years of age (mean age:31.84±13.14 years) presenting to the emergency with < 24 hours of abdominal trauma, were included in the study. Organs involved during blunt abdominal trauma were observed and frequency was recorded. Liver injuries were found in 48(42.28%) patients, intestinal injuries in 40(35.7%), splenic injuries in 32(28.5%), kidney injuries in 24(21.4%), pancreatic injuries in 8(7.1%) and stomach injuries in 4(3.5%) patients. Grade 4 liver injury was found in 80(71%) patients, Grade 2 and 3 splenic injuries in 56(50%) patients whereas 47(42%) patients had grade 1 kidney injury. Liver was found to be the most frequent organ involved, followed by intestine and spleen.

In vitro evaluation of antiviral activity of Sisybrium irio (Khaksi) against SARS-COV-2.

SARS-CoV-2 pandemic, drawn attention to the need of virus culture. In vitro SARS-COV-2 culture was performed to carry out therapeutic, environmental and virus genome studies. Isolation of virus from nasopharyngeal swab was performed by inoculating virus positive samples in available cell lines. SARS-CoV-2 topography was observed by using Scanning Electron Microscopy (SEM). Virus specificity was defined by serological confirmation through neutralization assay with COVID 19 convalescent sera. The SARS-COV-2 virus replicated successfully in Vero cell lines (both in E6 and CCL-81). The TCID50 and PFUs of isolated virus were defined as 107 TCID50/mL and 1.4 Х 106 pfu/mL respectively. The virus particles with the SARS-CoV morphology was <150ɳM size. Virus inhibition in presence of convalescent sera of COVID-19 patients was observed. Sisybrium irio (Khaksi) was found cytotoxic on Vero E6 cell line and its antiviral activity could not be established against SARS-COV-2 virus in vitro. Successful isolated and archived native SARS-COV-2 may be utilized further for therapeutic, environmental and virus genome sequencing studies.

Characterization of the multidrug efflux transporter styMdtM from Salmonella enterica serovar Typhi.

Salmonellae are foodborne pathogens and the major cause of gastroenteritis in humans. Salmonellae express multidrug efflux transporters that play a key role in their drug resistance, which is becoming an increasing problem for therapeutic intervention. Despite their biomedical importance, the mechanisms underlying substrate transport by multidrug efflux transporters remain poorly understood. Here, we describe the first characterization of a multidrug transporter belonging to the major facilitator superfamily from the genus Salmonella. We show that several clinical Salmonella Typhi (S. Typhi) isolates constitutively express the styMdtM (STY4874) gene, which encodes a known multidrug-resistance (MDR) transporter. Guided by the structure of the Escherichia coli (E. coli) homolog, we studied two residues critical for substrate transport, Asp25 and Arg111. Mutation of Asp25 to glutamate did not affect the transport function of styMdtM, whereas mutation to alanine reduced its transport activity, suggesting that a negative charge at this position is critical for substrate translocation across the membrane. Substrate-affinity measurements by intrinsic fluorescence spectroscopy showed that the Asp25Ala mutant retained its capacity to bind substrate, albeit at a lower level. Mutation of Arg111 to alanine resulted in a decrease in secondary structure content of the transporter, and mutation to lysine completely destabilized the structure of the transporter. A homology model of styMdtM suggests that Arg111 is important for stabilizing the transmembrane domain by mediating necessary interactions between neighboring helices. Together, our studies provide new structural and mechanistic insights into the Salmonella MDR transporter styMdtM.

Ornamental plants for the phytoremediation of heavy metals: Present knowledge and future perspectives.

Environmental matrices are polluted with the plethora of contaminants, and among these, the concerns related to heavy metals (HMs) are also included. Due to the low cost in a long-term application and environmental friendliness, the use of biological remediation has gained significant attention in recent decades. The use of ornamental plants (OPs) in the field of phytoremediation is scarcely reported, and the impacts of HMs on OPs have also not been investigated in great depth. The OPs mediated HMs remediation can simultaneously remove contaminants and bring improvement in aesthetics of the site. The biomass of OPs produced after such activities can be used and sold as pot plants, cut flowers, essential oils, perfumes, air fresheners production, metal phytomining, and feedstock in silk production. The OPs also present a lower risk of HMs bioaccumulation compared to crop plants. This review focuses on the current knowledge of HMs toxicity to OPs, their applicability advantages, methods to improve the tolerance of OPs with incremented HMs uptake, challenges in the field, and future application perspectives. The case studies realted to practical application of OPs, from China, Iran, India, Oman, Pakistan, and Turkey, were also discussed. This work fetches the inter-disciplinary features and understanding for the sustainable treatment of HMs in a new novel way, to which no previous review has focused.

The effect of acute complicated appendicitis on liver function test.

OBJECTIVES: To determine the diagnostic role of hyperbilirubinemia in acute appendicitis like suppurative and gangrenous appendicitis. METHODS: This observational study was conducted at Ward-3, Jinnah Postgraduate Medical Center (JPMC), Karachi from 1st June 2019 to 1st June 2020. Males and females above 12 years of age were included. Serum liver function tests and leukocyte counts were carried out. Appendectomies were done, the operative findings and histopathology reports were noted. Hyperbilirubinemia was related with the stages of appendicitis. Results were analyzed by SPSS version 25. RESULTS: There were one hundred twenty patients. Thirty-eight (31.66%) were females and eighty-two (68.33%) were males. Age range was 13 to 60 years. Ten patients (8.33%) were between 13 - 20 years, sixty five (54.16%) were 21 to 30 years, thirty (25%) were 31 - 40 years, ten (8.33%) were 41 - 50 years and five patients (4.17%) were above 50 years of age. Sixty-two (51.66%) patients had simple appendicitis and fifty-four (45%) had complicated appendicitis like suppurative (26.66%) and (16.66%) gangrenous appendicitis. Negative appendectomy was found in four (3.33%). Hyperbilirubinemia was found (100%) in gangrenous, (94.12%) in suppurative and (12.3%) in catarrhal appendicitis. Enzymes like Alanine transaminase and Aspartate transaminase were raised (50%) in gangrenous, (50%) in suppurative and (9.67%) in catarrhal appendicitis. TLC was raised in 112 (96.55%) out of 116 patients and total leukocyte count was normal in negative appendectomies. CONCLUSIONS: It is concluded that hyperbilirubinemia is strong diagnostic predictor for complicated appendicitis.

High-order harmonics generation in the plasmas produced on different rotating targets during ablation using 1 kHz and 100 kHz lasers.

We analyze the high-order harmonics generation using 1 kHz and 100 kHz lasers by ablating different rotating targets. We demonstrate the high average flux of short-wavelength radiation using the latter laser, while comparing the plasma formation conditions at different pulse repetition rates. The analysis of harmonic stability in the case of the 100 kHz experiments showed the two-fold decay of the 27th harmonic generating in silver plasma after 3.5×106 shots. The advantages of shorter pulse-induced ablation for the improvement of harmonic generation stability are demonstrated. Two-color pump of plasma, resonance enhancement of single harmonic, and quasi-phase matching studies are presented for 1 kHz laser applications. The formation of modulated multi-jet plasma on the plane and curved surfaces during ablation by 100 kHz pulses is demonstrated. In the case of the 25th harmonic of 1030 nm radiation (E=30 eV) generated during experiments in carbon plasma, at 100 kHz and 40 W average power of driving pulses, 0.4 mW of average power for single harmonic in the 40 nm spectral range was achieved.

Characterization of the highly immunogenic VP2 protrusion domain as a diagnostic antigen for members of Birnaviridae family.

Birnaviridae is a family of viruses (birnaviruses) which consists of four genera, members of which cause diseases in fish, birds, mollusks, and insects. The genome of birnaviruses encodes the highly immunogenic VP2 capsid protein. In order to demonstrate that the VP2 protein can be exploited as a diagnostic antigen for birnaviruses, we developed a lateral flow assay based on the surface-exposed VP2 protrusion domain of a representative birnavirus, infectious bursal disease virus (IBDV) of serotype 1 which causes the highly devastating infectious bursal disease in chickens. The biophysical characterization of the purified domain reveals that the domain predominantly consists of ß-sheets, exists in a trimeric form, and remains folded at high temperatures, making it suitable for diagnostic purposes. Owing to its highly immunogenic nature and excellent biophysical properties, we employed the VP2 protrusion domain in a gold nanoparticle-based lateral flow assay for rapid detection of anti-IBDV antibodies in serum samples of infected chickens. Our results indicate that the domain binds anti-IBDV antibodies with high specificity during laboratory testing and on-site testing. The lateral flow assay reported here yields comparable results in a qualitative manner as obtained through a commercial enzyme-linked immunosorbent assay (ELISA). As VP2 is a common capsid protein of birnaviruses, the lateral flow assay can be generalized for other birnaviruses, and members of Tetraviridae and Nodaviridae families which contain homologous VP2 capsid proteins.

C-Terminal Domain of the Human Zinc Transporter hZnT8 Is Structurally Indistinguishable from Its Disease Risk Variant (R325W).

The human zinc transporter 8 (hZnT8) plays important roles in the storage of insulin in the secretory vesicles of pancreatic ß cells. hZnT8 consists of a transmembrane domain, with its N- and C-termini protruding into the cytoplasm. Interestingly, the exchange of arginine to tryptophan at position 325 in the C-terminal domain (CTD) increases the risk of developing type 2 diabetes mellitus (T2D). In the present study, the CTDs of hZnT8 (the wild-type (WT) and its disease risk variant (R325W)) were expressed, purified, and characterized in their native forms by biophysical techniques. The data reveal that the CTDs form tetramers which are stabilized by zinc binding, and exhibit negligible differences in their secondary structure content and zinc-binding affinities in solution. These findings provide the basis for conducting further structural studies aimed at unravelling the molecular mechanism underlying the increased susceptibility to develop T2D, which is modulated by the disease risk variant.

Transcriptional regulation of drug resistance mechanisms in Salmonella: where we stand and what we need to know.

Salmonellae have evolved a wide range of molecular mechanisms to neutralize the effect of antibiotics and evade the host immune system response. These mechanisms are exquisitely controlled by global and local regulators and enable the pathogens to use its energy as per need and hence allow the pathogen to economize the consumption of energy by its cellular machinery. Several families that regulate the expression of different drug resistance genes are known; some of these are: the TetR family (which affects tetracycline resistance genes), the AraC/XylS family (regulators that can act as both transcriptional activators and repressors), two-component signal transduction systems (e.g. PhoPQ, a key regulator for virulence), mercury resistance Mer-R and multiple antibiotic resistance Mar-R regulators, LysR-type global regulators (e.g. LeuO) and histone-like protein regulators (involved in the repression of newly transferred resistance genes). This minireview focuses on the role of different regulators harbored by the Salmonella genome and characterized for mediating the drug resistance mechanisms particularly via efflux and influx systems. Understanding of such transcriptional regulation mechanisms is imperative to address drug resistance issues in Salmonella and other bacterial pathogens.

Environmental risk assessment of diclofenac residues in surface waters and wastewater: a hidden global threat to aquatic ecosystem.

Pharmaceuticals are chemical compounds employed as medicinal drugs. They have severe physic-chemical properties which make them destructive for non-target species. Consequently, their continuous addition in the environment may pose hazardous effects. Among these, diclofenac (DCF), a non-steroidal anti-inflammatory drug (NSAID), is extensively used in Pakistan which may lead to its accumulation in both terrestrial and aquatic environment. Present study aims to assess the presence and concentration of pharmaceutically active drug (DCF) in surface water and wastewater of twin cities of Pakistan (Rawalpindi and Islamabad). For this purpose, a validated high-performance liquid chromatography (HPLC) method was adopted involving solid-phase extraction procedure. Wastewater samples were collected from various sites of Rawalpindi and Islamabad. Results of HPLC analysis revealed that DCF was extant with considerably high concentration, not only in wastewater but also in surface water samples. Concentrations as high as 216 µg L-1 was detected in Rawat industrial area and low as 8 µg L-1 was detected in dairy farm wastewater samples collected from Taramri. However, maximum DCF levels in residential wastewater and hospital wastewater were detected to be 105 µg L-1 and 34 µg L-1, respectively. Moreover, the highest detected level (116 µg L-1) was found in surface water of Sawan River. Further, results of ecological risk assessment revealed its possible toxic effects of DCF on various aquatic organisms.

Synthesis, characterization and antimicrobial activity of norfloxacin based acetohydrazides.

The drug resistance phenomenon in microbes is resulting in the ineffectiveness of available drugs to treat the infections. Thus, there is a continued need to discover new molecules to combat the drug resistance phenomenon. Norfloxacin is a fluoroquinolone antibiotic that is used for the treatment of urinary tract infections. In this research work, norfloxacin is structurally modified by hybridizing with a range of substituted acetohydrazidic moieties through a multistep reaction. The first step involves the coupling of norfloxacin 1 with methyl chloroacetate followed by the treatment with hydrazine hydrate to result in corresponding acetohydrazide 3. A range of substituted benzaldehydes were reacted with the acetohydrazide to form the targeted series of norfloxacin derivatives 4a-i. The final compounds were screened for antimicrobial activity. Among the tested compounds, 4c, 4d, 4e and 4f displayed better antifungal activity against F.avenaceum, while compound 4c and 4e were active against F. bubigeum.