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The global community is struggling with the highly contagious COVID-19. Returning to \normal life" now poses risks, and the use of appropriate protective measures has become necessary to continue daily life and protect public health. The main protective measures to prevent transmission of COVID-19 are masks, soaps and disinfectants. Because coronavirus is a \lipid-enveloped virus", it is very sensitive to lipid-dissolving chemicals and can therefore be effectively removed by washing hands sufficiently with soap and water. However, using an alcohol-based disinfectant is a more viable option for outdoor use. Alcohol-based disinfectants are inexpensive, immediately effective, easy to use and better tolerated by the skin compared to other disinfectants. WHO recommends disinfectants containing 75% isopropanol or 80% ethanol as highly effective in inactivating the SARS-CoV-2-virus. The current review discusses the role of alcohol-based hand sanitizers (ABHS) in preventing the spread of viruses, their side effects on human health, and suggests the use of alcohol-based sanitizers as potentially effective in combating the current epidemic.

Biochemistry is implemented in undergraduate medical school from the very beginning of the curriculum. Achieving a high level of competence in this area strongly influences academic success throughout the entire program. Due to the evaporating nature of this subject, medical students struggle to retain biochemistry concepts across the two years of their preclinical courses, especially while preparing for their board examinations. Therefore, the curriculum should be designed strategically to effectively implement the ever-growing field of biochemistry and metabolic pathways across the preclinical years of medical education. We propose a broadened integration of biochemistry by providing clinically correlated metabolic concepts which spiral across multiple domains, thus deepening and solidifying students’ understanding of pathology and etiology. This approach may help medical students retain their subject expertise and understand the complex material in the clinical context to minimize rote memorization. We hope to encourage medical educators, course directors, and curriculum administrators to utilize these tips to augment their biochemistry instruction in medical education.

Co-infections of mammalian hosts with intestinal helminths and bacterial pathogens are common, especially in areas with inadequate sanitation. Interactions between co-infecting species and host microbiota can cause significant changes in host immunity, disease severity, and pathogen transmission, requiring unique treatment for each case. A greater understanding of the influences of parasite-bacteria co-infections will improve diagnosis and therapeutic approaches to control infectious diseases. To study the influence of the trematode parasite Echinostoma caproni on commensal and pathogenic bacteria in the mouse gut, we examined the abundance of intestinal lactic acid bacteria and Salmonella enterica serovar Typhimurium in control mice not exposed to E. caproni (P-) or S. Typhimurium (S-), E. caproni-infected (P+S-), S. Typhimurium-infected (P-S+), and E. caproni-S. Typhimurium co-infected (P+S+) mice, and determined bacterial burdens in the livers and spleens of the P-S+ and P+S+ mice. We also examined a subset of P+S- and P+S+ mice for survival and the relative location of E. caproni in the small intestine. The numbers of presumptive lactic acid bacteria were significantly higher in the P+S+ and P-S+ mice compared to the uninfected mice, and S. Typhimurium colonization in the liver and spleen was significantly reduced in the P+S+ mice compared to the P-S+ mice. Echinostoma caproni were located anteriorly in the intestine of P+S- mice, while in the P+S+ mice, the parasites were distributed more posteriorly. Survival of E. caproni was unaffected in either group. The results of our study suggest that E. caproni facilitates a higher abundance of presumptive lactic acid bacteria in the mouse intestine and reduces colonization of S. Typhimurium in the liver and spleen of the co-infected host.

Comparative genomic sequencing of laboratory-derived vancomycin-intermediate Staphylococcusaureus (VISA) (MM66-3 and MM66-4) revealed unique mutations in both MM66-3 (in apt and ssaA6), and MM66-4 (in apt and walK), compared to hetero-VISA parent strain MM66. Transcriptional profiling revealed that both MM66 VISA shared 79 upregulated genes and eight downregulated genes. Of these, 30.4% of the upregulated genes were associated with the cell envelope, whereas 75% of the downregulated genes were associated with virulence. In concordance with mutations and transcriptome alterations, both VISA strains demonstrated reduced autolysis, reduced growth in the presence of salt and reduced virulence factor activity. In addition to mutations in genes linked to cell wall metabolism (ssaA6 and walK), the same mutation in apt which encodes adenine phosphoribosyltransferase, was confirmed in both MM66 VISA. Apt plays a role in both adenine metabolism and accumulation and both MM66 VISA grew better than MM66 in the presence of adenine or 2-fluoroadenine indicating a reduction in the accumulation of these growth inhibiting compounds in the VISA strains. MM66 apt mutants isolated via 2-fluoroadenine selection also demonstrated reduced susceptibility to the cell wall lytic dye Congo red and vancomycin. Finding that apt mutations contribute to reduced vancomycin susceptibility once again suggests a role for altered purine metabolism in a VISA mechanism.

Microbial contamination of water is a significant burden to public health, particularly in low- and middle-income countries. To develop an affordable and user-friendly method for detecting microbial water contamination in resource-limited settings, a business card-sized device, named the MicroBioPAD, was developed using filter paper saturated with the chromogenic sugar X-Gal. This device was compared to the standard most probable number (MPN) test and a plate culture-based test to assess fecal pollution of water in Nepal. A total of 120 water samples were collected from the Central (Kathmandu) and Southern (Chitwan) regions; these included 36 samples from three major rivers and 84 samples from various drinking water sources. The MPN and plate culture tests revealed fecal contamination in 93.1 and 27.3% of the samples collected in Kathmandu and Chitwan, respectively, with the levels of E. coli ranging from < 3 to ≥ 1100 CFU/100 ml in the Kathmandu water samples and < 3 to 160 CFU/100 ml in the Chitwan water samples. Compared to the standard culture-based tests, the MicroBioPAD produced positive results within a shorter time (24 h) and showed a 100% accuracy of detection for samples containing ≥ 3 E. coli CFU/ml, suggesting a detection limit of 3 E. coli CFU/ml when using only 100 μl of the sample. The MicroBioPAD will be useful as a relatively faster semi-quantitative device to determine water suitability for bathing, cleaning, and recreational purposes.

The greatest pandemic of the century, COVID-19, is an ongoing global public health problem. With a clinically approved treatment available only for those who are acutely ill and are hospitalized, the control of this disease in the general population is still largely dependent on the preventive measures issued by the World Health Organization. Among the general control measures other than immunization with the COVID-19 vaccines, handwashing with soap and water has been emphasized the most because it is cost-effective and easily accessible to the general public. Studies have reported that soaps offer unique chemical properties that can completely destroy enveloped viruses. However, the general public seems to be still uncertain about whether soaps can shield us from a highly contagious disease such as COVID-19. In an attempt to help eliminate the uncertainty, we analyzed the mechanisms underlying the efficacy of soap and its prospect for preventing the spread of COVID-19. In this paper, we provide an overview of the history and characteristics of the SARS-CoV-2 virus, the current global COVID-19 situation, the possible mechanisms of the deactivation of viruses by soaps, and the potential effectiveness of soap in eliminating coronaviruses including SARS-CoV-2.

Background This is the first study to determine whether nonskid slipper socks in contact with the hospital floor and worn into bed contaminate bed linen. Purpose The main purpose of the study was to determine whether contamination of hospital linen occurred with bacteria transferred from the soles of nonskid slipper socks that have touched the floor. Methods This study mimicked real patients walking on a hospital floor wearing slipper socks and getting back into bed with the slipper socks on. Swab samples were collected from the surfaces of the hospital floor, nonskid slipper sock bottoms, and bed linen in 2 Midwestern hospitals. From the samples, bacterial isolates were identified and tested for antibiotic resistance. Results Isolates obtained from the samples were identified on all 3 surfaces at both hospitals, indicating spread of the bacteria from floor to the bed linen via the nonskid slipper socks. Antibiotic sensitivity test revealed that a significant number of isolates collected were resistant to at least 2 antibiotics tested. Conclusion This study demonstrates cross-contamination of bed linen with potentially pathogenic bacteria present on the hospital floor via contact with patient-worn nonskid slipper socks. A simple practice change regarding the wearing of slipper socks could play an important role in preventing pathogen transfer to the bed linen. Awareness of the likelihood of hand contamination after touching the sock bottoms that have come in contact with the hospital floor should also be considered.

The Gram-positive bacterium Staphylococcus aureus is well known for its ability to develop resistance to various antimicrobial substances. Methicillin-resistant S. aureus (MRSA), a cause of nosocomial infections worldwide, is becoming increasingly resistant to the glycopeptide antibiotic vancomycin, one of few antibiotics used to treat serious multiple-antibiotic-resistant staphylococcal infections. With the increase in the number of MRSA strains showing reduced sensitivity to vancomycin, it has become important to investigate alternative treatment options. In this study, we examined the effects of five metals: silver, copper, arsenate, zinc, and cadmium on the growth of a clinical MRSA strain MM66 demonstrating heterogeneous intermediatelevel resistance to vancomycin. Disc diffusion and gradient plate experiments were used to compare the metal susceptibility levels of strain MM66 to that of the methicillin-resistant S. aureus laboratory control strain. MM66 grew less successfully when exposed to metals, and showed an overall increased level of susceptibility to metals compared to the laboratory control strain. Of the metals tested, silver exerted the highest inhibitory effect on the growth of MM66.

Salmonella enterica serovar Typhimurium utilizes molecular hydrogen as a substrate in various respiratory pathways, via H 2 -uptake enzymes termed Hya, Hyb, and Hyd. A different hydrogenase, the hydrogen-evolving Hyc enzyme, removes excess reductant during fermentative growth. Virulence phenotypes conferred by mutations in hyc genes, either alone or in combination with mutations in the H 2 -uptake enzyme genes, are addressed. Anaerobically grown Δ hycB or Δ hycC single-deletion strains were more sensitive to acid than the wild-type strain, but the Δ hyc strains were like the virulent parent strain with respect to both mouse morbidity and mortality and in organ burden numbers. Even fecal-recovery numbers for both mutant strains at several time points prior to the animals succumbing to salmonellosis were like those seen with the parent. Neither hydrogen uptake nor evolution of the gas was detected in a hydrogenase quadruple-mutant strain containing deletions in the hya , hyb , hyd , and hyc genes. As previously described, a strain lacking all H 2 -uptake ability was severely attenuated in its virulence characteristics, and the quadruple-mutant strain had the same (greatly attenuated) phenotype. While H 2 levels were greatly reduced in ceca of mice treated with antibiotics, both the Δ hycB and Δ hycC strains were still like the parent in their ability to cause typhoid salmonellosis. It seems that the level of H 2 produced by the pathogen (through formate hydrogen lyase [FHL] and Hyc) is insignificant in terms of providing respiratory reductant to facilitate either organ colonization or contributions to gut growth leading to pathogenesis.

A survey of 152 methicillin-resistant Staphylococcus aureus (MRSA) strains from medical centers in Las Cruces, NM, and El Paso, TX, revealed the presence of spa types 2 and 24 (clone USA100) and spa type 1 (clone USA300-0114). Las Cruces MRSA displayed relatively high vancomycin MICs, and one hetero-vancomycin-intermediate S. aureus strain was identified.

We report the draft genome sequences of three vancomycin-susceptible methicillin-resistant Staphylococcus aureus strains. S. aureus strain MV8 is a sequence type 8 (ST-8) staphylococcal cassette chromosome mec element type IV (SCC mec IV) derivative, while the other two strains ( S. aureus MM25 and MM61) are ST-5 SCC mec II strains. MM61 is also closely related to the heterogeneous vancomycin-intermediate S. aureus strain MM66.

The draft genomes of heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) strain MM66 and MM66 isolates demonstrating altered vancomycin resistance levels were produced in an effort to provide information on mutations contributing to the vancomycin resistance levels observed in these strains .

Helicobacter hepaticus open reading frame HH0352 was identified as a nickel-responsive regulator NikR. The gene was disrupted by insertion of an erythromycin resistance cassette. The H. hepaticus nikR mutant had five- to sixfold higher urease activity and at least twofold greater hydrogenase activity than the wild-type strain. However, the urease apo-protein levels were similar in both the wild-type and the mutant, suggesting the increase in urease activity in the mutant was due to enhanced Ni-maturation of the urease. Compared with the wild-type strain, the nikR strain had increased cytoplasmic nickel levels. Transcription of nikABDE (putative inner membrane Ni transport system) and hh0418 (putative outer membrane Ni transporter) was nickel- and NikR-repressed. Electrophoretic mobility shift assays (EMSAs) revealed that purified HhNikR could bind to the nikABDE promoter (P(nikA)), but not to the urease or the hydrogenase promoter; NikR-P(nikA) binding was enhanced in the presence of nickel. Also, qRT-PCR and EMSAs indicated that neither nikR nor the exbB-exbD-tonB were under the control of the NikR regulator, in contrast with their Helicobacter pylori homologues. Taken together, our results suggest that HhNikR modulates urease and hydrogenase activities by repressing the nickel transport/nickel internalization systems in H. hepaticus, without direct regulation of the Ni-enzyme genes (the latter is the case for H. pylori). Finally, the nikR strain had a two- to threefold lower growth yield than the parent, suggesting that the regulatory protein might play additional roles in the mouse liver pathogen.

Salmonella enterica serovar Typhimurium can utilize molecular hydrogen for growth and amino acid transport during anaerobic growth. Via microarray we identified H 2 gas-affected gene expression changes in Salmonella . The addition of H 2 caused altered expression of 597 genes, of which 176 genes were upregulated and 421 were downregulated. The significantly H 2 -upregulated genes include those that encode proteins involved in the transport of iron, manganese, amino acids, nucleosides, and sugars. Genes encoding isocitrate lyase ( aceA ) and malate synthase ( aceB ), both involved in the carbon conserving glyoxylate pathway, and genes encoding the enzymes of the d -glucarate and d -glycerate pathways ( gudT , gudD , garR , garL , garK ) are significantly upregulated by H 2 . Cells grown with H 2 showed markedly increased AceA enzyme activity compared to cells without H 2 . Mutant strains with deletion of either aceA or aceB had reduced H 2 -dependent growth rates. Genes encoding the glutamine-specific transporters ( glnH , glnP , glnQ ) were upregulated by H 2 , and cells grown with H 2 showed increased [ 14 C]glutamine uptake. Similarly, the mannose uptake system genes ( manX , manY ) were upregulated by H 2, and cells grown with H 2 showed about 2.0-fold-increased [ 14 C] d -mannose uptake compared to the cells grown without H 2 . Hydrogen stimulates the expression of genes involved in nutrient and carbon acquisition and carbon-conserving pathways, linking carbon and energy metabolism to sustain H 2 -dependent growth.

It is known that multiple genome-wide transcriptional changes often accompany the development of antimicrobial resistance and occur in response to challenge with antimicrobial agents. We now show that inactivation of the staphylococcal accessory gene regulator sarA, which controls at least tens of genes in Staphylococcus aureus, leads to dramatic reductions in vancomycin and ciprofloxacin resistance in vancomycin-intermediate and ciprofloxacin-resistant strains of S. aureus. This is particularly evident when judged by antimicrobial-gradient plate analysis or population analysis profiles. Whilst the intact sarA cistron is required for full vancomycin resistance expression by vancomycin-intermediate S. aureus (VISA), sarA expression as determined by quantitative real-time polymerase chain reaction was found to be VISA strain-dependent. Reductions in vancomycin resistance expression levels following sarA inactivation do not necessarily include an alteration in autolysis. Expression of sarR, the negative regulator of sarA, was downregulated in two VISA mutants, and transcription of the alternative sigma factor sigB was downregulated in one VISA strain. This study contributes to a growing body of evidence demonstrating the importance of loci previously identified to control virulence in the regulation of clinically relevant antibiotic resistance mechanisms.

Aims: To identify factors associated with the Staphylococcus aureus pine-oil disinfectant-reduced-susceptibility (PDRS) mechanism and to describe one possible PDRS model. Methods and Results: Comparative genomic sequencing (CGS) and microarray analysis were utilized to detect mutations and transcriptome alterations that occur in a S. aureus PDRS mutant. Mutant analysis, antimicrobial gradient plates, growth studies and 3-hydroxy-3-methylglutaryl coenzyme A synthase assays were then performed to confirm the biological consequences of the ‘omics’ alterations detected in a PDRS mutant. CGS uncovered three mutations in a PDRS mutant in a(n): alcohol dehydrogenase (adh), catabolite control protein A (ccpA) and an NADPH-flavin oxidoreductase (frp). These mutations lead to increased growth rates; increased transcription of an NAD-dependent d-lactate dehydrogenase gene (ddh); and increased flux through the mevalonate pathway. PDRS mutants demonstrated reduced susceptibility to bacitracin and farnesol, and one PDRS mutant displayed upregulation of bacA, a bacitracin-resistance gene. Collectively, this evidence demonstrates altered undecaprenol metabolism in PDRS mutants. Conclusions: The PDRS mechanism proposed results from increased catabolic capabilities and increased flux through the mevalonate pathway as well as altered bactoprenol physiology. Significance and Impact of the Study: A novel mechanism that bacteria utilize to overcome the killing effects of PD formulations is proposed that is unique from the PDRS mechanism of the enterobacteraciae.