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Gut bacteria of animals living in polluted environments exhibit broad-spectrum antibacterial activities

Akbar N, Siddiqui R, Sagathevan K, Khan NA

Int Microbiol, 2020 Nov;23(4):511-526.
PMID: 32124096 DOI: 10.1007/s10123-020-00123-3

Infectious diseases, in particular bacterial infections, are the leading cause of morbidity and mortality posing a global threat to human health. The emergence of antibiotic resistance has exacerbated the problem further. Hence, there is a need to search for novel sources of antibacterials. Herein, we explored gut bacteria of a variety of animals living in polluted environments for their antibacterial properties against multi-drug resistant pathogenic bacteria. A variety of species were procured including invertebrate species, Blaptica dubia (cockroach), Gromphadorhina portentosa (cockroach), Scylla serrata (crab), Grammostola rosea (tarantula), Scolopendra subspinipes (centipede) and vertebrate species including Varanus salvator (water monitor lizard), Malayopython reticulatus (python), Cuora amboinensis (tortoise), Oreochromis mossambicus (tilapia fish), Rattus rattus (rat), Gallus gallus domesticus (chicken) and Lithobates catesbeianus (frog). Gut bacteria of these animals were isolated and identified using microbiological, biochemical, analytical profiling index (API) and through molecluar identification using 16S rRNA sequencing. Bacterial conditioned media (CM) were prepared and tested against selected Gram-positive and Gram-negative pathogenic bacteria as well as human cells (HaCaT). The results revealed that CM exhibited significant broad-spectrum antibacterial activities. Upon heat inactivation, CM retained their antibacterial properties suggesting that this effect may be due to secondary metabolites or small peptides. CM showed minimal cytotoxicity against human cells. These findings suggest that gut bacteria of animals living in polluted environments produce broad-spectrum antibacterial molecule(s). The molecular identity of the active molecule(s) together with their mode of action is the subject of future studies which could lead to the rational development of novel antibacterial(s).

Matched MeSH terms: Anti-Bacterial Agents/pharmacology*
Molecular epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) among veterinary students and personnel at a veterinary hospital in Malaysia

Aklilu E, Zunita Z, Hassan L, Cheng CH

Vet Microbiol, 2013 Jun 28;164(3-4):352-8.
PMID: 23523336 DOI: 10.1016/j.vetmic.2013.02.030

In this study, we report the molecular epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) among veterinary students and personnel in Malaysia. Nasal and oral swabs were collected from 103 veterinary medicine students and 28 personnel from a veterinary hospital. Antibiotic sensitivity test (AST), minimum inhibitory concentration (MIC) test, and PCR amplifications of nucA and mecA gene were performed. Molecular characterization of the isolates was conducted using multilocus sequence typing (MLST), staphylococcal protein A gene (spa) typing, and pulsed-field gel electrophoresis (PFGE). Results from MLST show the presence of the pandemic and widespread MRSA clones, ST5 and ST59. Spa gene typing revealed spa type t267 which has a wide geographical distribution. A new spa type, t5697 was found in this study. Fingerprint analysis by using PFGE show heterogeneity of the isolates. These findings affirm the importance of MRSA in veterinary settings and underscore the need for further extensive research to devise contextual control and prevention strategies.

Matched MeSH terms: Anti-Bacterial Agents/pharmacology
Fulltext Phenotypic and genotypic characterization of methicillin-resistant Staphylococcus aureus (MRSA) isolated from dogs and cats at University Veterinary Hospital, Universiti Putra Malaysia

Aklilu E, Zunita Z, Hassan L, Chen HC

Trop Biomed, 2010 Dec;27(3):483-92.
PMID: 21399590

Methicillin-resistant Staphylococcus aureus (MRSA) is known to cause nosocomial infections and is now becoming an emerging problem in veterinary medicine. The objective of the study was to determine the presence of MRSA in 100 cats and dogs sampled between November 2007 and April 2008 at the University Veterinary Hospital, Universiti Putra Malaysia. MRSA was detected in 8% of pets sampled. Ten percent (5/50) and 6% (3/50) of the isolates were from dogs and cats, respectively. All MRSA isolates possessed the mecA gene and were found to be resistant to at least three antimicrobials with a minimum of Oxacillin MIC of 8 μg/mL. One isolate (CT04) had an extremely high MIC of >256 μg/mL. The MLST type ST59 found in this study have been reported earlier from Singapore and other countries as a strain from animal and community-associated MRSA respectively. Pulsed-field gel electrophoresis revealed five pulsotypes. Two isolates from cats (CT27 and CT33) and three isolates from dogs (DG16, DG20, and DG49) were respectively assigned to pulsotypes B and D. The study suggests that cats and dogs in Malaysia are potential reservoirs for MRSA.

Matched MeSH terms: Anti-Bacterial Agents/pharmacology
Urinary tract infection and non-ruptured acute appendicitis association: Uro-pathogens findings

Al Fraijat B, Al-Tawarah NM, Khlaifat AM, Qaralleh H, Khleifat KM, M A, et al.

Trop Biomed, 2019 Sep 01;36(3):620-629.
PMID: 33597484

Urinary Tract Infections (UTIs) consider as the most common infections worldwide, with higher risk in patients experienced Acute Appendicitis (AA). The purpose of this study was, to investigate the bacterial profile of UTIs in patients with non-ruptured AA postsurgically, and to assess age- and gender-related links of all AA cases in Karak region, Jordan. Urine samples obtained from 46 cases (32 male and 14 female) aged between 16-70 years were diagnosed as non-ruptured AA, following with isolation and characterization of isolated bacteria. Out of 46 AA cases, uropathogens isolated from 25 (54.3%) UTI cases. Out of these isolates; 42 (73.7%) were gram-negative isolates and 15 (26.3%) were gram-positive bacteria. The percentage of isolates were E. coli (26.3%), Enterobacter species (21%), Enterococcus faecalis and Klebsiella pneumoniea (10.5%) for each, Streptococcus saprophytics and Pseudomonas aeruginosa (7%) for each, Yersinia spp. and S. milleri (8.8%). Out of UTI cases, 20 cases (80%) possessed mixed culture, each of them had at least one of Enterobacterial species. i.e. Enterobacter spp. or E. coli or both. More precisely, out of all these positivecases, 2 cases had pure gram positive-bacterial infection (8%), while pure gram negative bacterial infection comprised 48% of them and the rest (44%) were mixed (gram-negative and gram-positive) bacterial infection. Moreover, study revealed a high prevalence rate of AA cases 24 (52.2%) in the ages of 16-22 years, then declining the rate with increasing the age, reaching the lowest rate (4.3%) in ages of 60-70. In addition to age factor, the males significantly more susceptible to AA cases than females by 2.2-fold. Antibiotic sensitivity test revealed high resistance capability of E. coli to the most used antibiotics except for nitrofurantoin. Bacterial isolates showing sensitivity against ciprofloxacin, trimethoprim/sulfamethoxazole, amoxicillin-Clavulanic acid and nitrofurantoin, with a superiority for the first two. Results demonstrate high prevalence rate of UTIs in patients with AA. For avoiding, the needless use of antibiotics through sticking to our accountability as healthcare provisioner to pursuit the antimicrobial management.

Matched MeSH terms: Anti-Bacterial Agents/pharmacology
Fulltext Antibiotic resistance before, during, and after the COVID-19 pandemic: a retrospective study

Al Sulayyim H, Ismail R, Al Hamid A, Mohammed B, Abdul Ghafar N

J Infect Dev Ctries, 2024 Mar 31;18(3):371-382.
PMID: 38635620 DOI: 10.3855/jidc.19071

INTRODUCTION: Prevalence of antibiotic resistance (AR) during the coronavirus 2019 (COVID-19) pandemic was higher than pre-pandemic times. This study determined the prevalence and patterns of AR among Gram-positive and negative bacteria before, during and after COVID-19 in Saudi Arabia and identified the associated factors.
METHODOLOGY: A retrospective cross-sectional study was employed to identify patients with positive AR bacteria between March 2019 and March 2022. The bacterial isolates and patients' data were identified from laboratory and medical records departments retrospectively. Binary logistic regression analysis was performed to identify the factors associated with AR and deaths. Multinominal logistic regression was applied to confirm the factors associated with AR classification.
RESULTS: AR Gram-negative bacteria decreased during and after the pandemic. However, S. aureus showed a negligible increase in resistance rate after pandemic, while E. faecium, recorded a higher-than-average resistance rate during the pandemic. The prevalence of pan drug resistance (PDR) during the pandemic (85.7%) was higher than before (0%) and after (14.3%), p = 0.001. The length of stay and time were significant predictors for AR classification. The odds of multi drug resistance (MDR) development to PDR during the pandemic were 6 times higher than before and after (OR = 6.133, CI =, p = 0.020). Age, nationality, COVID-19 infection, smoking, liver disease, and type and number of bacteria were associated with death of patients with positive AR.
CONCLUSIONS: Further studies are recommended to explore the prevalence of PDR and to justify the increased rates of E. faecium AR during the COVID-19 pandemic.

Matched MeSH terms: Anti-Bacterial Agents/pharmacology
Fulltext Antifilarial and Antibiotic Activities of Methanolic Extracts of Melaleuca cajuputi Flowers

Al-Abd NM, Nor ZM, Mansor M, Hasan MS, Kassim M

Korean J Parasitol, 2016 Jun;54(3):273-80.
PMID: 27417081 DOI: 10.3347/kjp.2016.54.3.273

We evaluated the activity of methanolic extracts of Melaleuca cajuputi flowers against the filarial worm Brugia pahangi and its bacterial endosymbiont Wolbachia. Anti-Wolbachia activity was measured in worms and in Aedes albopictus Aa23 cells by PCR, electron microscopy, and other biological assays. In particular, microfilarial release, worm motility, and viability were determined. M. cajuputi flower extracts were found to significantly reduce Wolbachia endosymbionts in Aa23 cells, Wolbachia surface protein, and microfilarial release, as well as the viability and motility of adult worms. Anti-Wolbachia activity was further confirmed by observation of degraded and phagocytized Wolbachia in worms treated with the flower extracts. The data provided in vitro and in vivo evidence that M. cajuputi flower extracts inhibit Wolbachia, an activity that may be exploited as an alternative strategy to treat human lymphatic filariasis.

Matched MeSH terms: Anti-Bacterial Agents/pharmacology*
Synthesis, antibacterial activity and cytotoxicity of new fused pyrazolo[1,5-a]pyrimidine and pyrazolo[5,1-c][1,2,4]triazine derivatives from new 5-aminopyrazoles

Al-Adiwish WM, Tahir MI, Siti-Noor-Adnalizawati A, Hashim SF, Ibrahim N, Yaacob WA

Eur J Med Chem, 2013 Jun;64:464-76.
PMID: 23669354 DOI: 10.1016/j.ejmech.2013.04.029

New 5-aminopyrazoles 2a-c were prepared in high yields from the reaction of known α,α-dicyanoketene-N,S-acetals 1a-c with hydrazine hydrate under reflux in ethanol. These compounds were utilized as intermediates to synthesize pyrazolo[1,5-a]-pyrimidines 3a-c, 4a-d, 5a-c, and 6a-c, as well as pyrazolo[5,1-c][1,2,4]triazines 7a-c and 8a-c, by the reaction of 2-[bis(methylthio)methylene]malononitrile, α,α-dicyanoketene-N,S-acetals 1a-b, acetylacetone, acetoacetanilide as well as acetylacetone, and malononitrile, respectively. Furthermore, cyclization of 2a-c with pentan-2,5-dione yielded the corresponding 5-pyrrolylpyrazoles 9a-c. Moreover, fusion of 2a-c with acetic anhydride resulted in the corresponding 1-acetyl-1H-pyrazoles 10a-c. The antibacterial activity and cytotoxicity against Vero cells of several selected compounds are also reported.

Matched MeSH terms: Anti-Bacterial Agents/pharmacology*
Optimizing of pharmaceutical active compounds biodegradability in secondary effluents by β-lactamase from Bacillus subtilis using central composite design

Al-Gheethi A, Noman E, Radin Mohamed RMS, Ismail N, Bin Abdullah AH, Mohd Kassim AH

J Hazard Mater, 2019 03 05;365:883-894.
PMID: 30497042 DOI: 10.1016/j.jhazmat.2018.11.068

Biodegradation of pharmaceuticals active compounds (PACs) in secondary effluents by using B. subtilis 2012WTNC as a function of β-lactamase was optimized using response surface methodology (RSM) designed by central composite design (CCD). Four factors including initial concentration of bacteria (1-6 log10 CFU mL-1), incubation period (1-14 days), incubation temperature (20-40 °C) and initial concentration of PACs (1-5 mg L-1) were investigated. The optimal operating factors for biodegradation process determined using response surface methodology (RSM) was recorded with 5.57 log10 CFU mL-1 of B. subtilis, for 10.38 days, at 36.62 °C and with 4.14 mg L-1 of (cephalexin/amoxicillin) with R2 coefficient of 0.99. The biodegradation was 83.81 and 93.94% respectively. The relationship among the independent variables was significant (p

Matched MeSH terms: Anti-Bacterial Agents/pharmacology
Fulltext Down-top nanofabrication of binary (CdO)x (ZnO)1-x nanoparticles and their antibacterial activity

Al-Hada NM, Mohamed Kamari H, Abdullah CAC, Saion E, Shaari AH, Talib ZA, et al.

Int J Nanomedicine, 2017;12:8309-8323.
PMID: 29200844 DOI: 10.2147/IJN.S150405

In the present study, binary oxide (cadmium oxide [CdO])x (zinc oxide [ZnO])1-x nanoparticles (NPs) at different concentrations of precursor in calcination temperature were prepared using thermal treatment technique. Cadmium and zinc nitrates (source of cadmium and zinc) with polyvinylpyrrolidone (capping agent) have been used to prepare (CdO)x (ZnO)1-x NPs samples. The sample was characterized by X-ray diffraction (XRD), scanning electron microscopy, energy-dispersive X-ray (EDX), transmission electron microscopy (TEM), and Fourier transform infrared (FTIR) spectroscopy. XRD patterns analysis revealed that NPs were formed after calcination, which showed a cubic and hexagonal crystalline structure of (CdO)x (ZnO)1-x NPs. The phase analysis using EDX spectroscopy and FTIR spectroscopy confirmed the presence of Cd and Zn as the original compounds of prepared (CdO)x (ZnO)1-x NP samples. The average particle size of the samples increased from 14 to 33 nm as the concentration of precursor increased from x=0.20 to x=0.80, as observed by TEM results. The surface composition and valance state of the prepared product NPs were determined by X-ray photoelectron spectroscopy (XPS) analyses. Diffuse UV-visible reflectance spectra were used to determine the optical band gap through the Kubelka-Munk equation; the energy band gap was found to decrease for CdO from 2.92 to 2.82 eV and for ZnO from 3.22 to 3.11 eV with increasing x value. Additionally, photoluminescence (PL) spectra revealed that the intensity in PL increased with an increase in particle size. In addition, the antibacterial activity of binary oxide NP was carried out in vitro against Escherichia coli ATCC 25922 Gram (-ve), Salmonella choleraesuis ATCC 10708, and Bacillus subtilis UPMC 1175 Gram (+ve). This study indicated that the zone of inhibition of 21 mm has good antibacterial activity toward the Gram-positive B. subtilis UPMC 1175.

Matched MeSH terms: Anti-Bacterial Agents/pharmacology*
The effect of Malaysian honey and its major components on the proliferation of cultured fibroblasts

Al-Jadi AM, Kanyan Enchang F, Mohd Yusoff K

Turk J Med Sci, 2014;44(5):733-40.
PMID: 25539538

BACKGROUND/AIM: To examine, for the first time, the effect of a selected Malaysian honey and its major components on the proliferation of cultured fibroblasts.
MATERIALS AND METHODS: Honey and some of its components, which include the sugars, the proteins, the hydrogen peroxide produced, and the phenolics, were exposed to cultured fibroblasts. The MTT colorimetric assay was used to assess cell viability and proliferation.
RESULTS: The stimulatory effect of honey on fibroblast proliferation was observed to be time- and dose-dependent. The continuous production of hydrogen peroxide by the honey-glucose oxidase system also acts to stimulate cell proliferation in a time- and dose-dependent manner. The presence of phenolics with antioxidant properties, on the other hand, renders protection to the cells against the toxic effect of hydrogen peroxide. However, the presence of a growth factor-like substance in honey could not be ascertained.
CONCLUSION: For the first time, honey and its major components were shown to exert stimulatory effects on cultured fibroblasts. Honey is therefore potentially useful in medicinal practices.

Matched MeSH terms: Anti-Bacterial Agents/pharmacology
Machine learning and molecular simulation ascertain antimicrobial peptide against Klebsiella pneumoniae from public database

Al-Khdhairawi A, Sanuri D, Akbar R, Lam SD, Sugumar S, Ibrahim N, et al.

Comput Biol Chem, 2023 Feb;102:107800.
PMID: 36516617 DOI: 10.1016/j.compbiolchem.2022.107800

Antimicrobial peptides (AMPs) are short peptides with a broad spectrum of antimicrobial activity. They play a key role in the host innate immunity of many organisms. The growing threat of microorganisms resistant to antimicrobial agents and the lack of new commercially available antibiotics have made in silico discovery of AMPs increasingly important. Machine learning (ML) has improved the speed and efficiency of AMP discovery while reducing the cost of experimental approaches. Despite various ML platforms developed, there is still a lack of integrative use of ML platforms for AMP discovery from publicly available protein databases. Therefore, our study aims to screen potential AMPs with antibiofilm properties from databases using ML platforms, followed by protein-peptide molecular docking analysis and molecular dynamics (MD) simulations. A total of 5850 peptides classified as non-AMP were screened from UniProtKB and analyzed using various online ML platforms (e.g., CAMPr3, DBAASP, dPABBs, Hemopred, and ToxinPred). Eight potential AMP peptides against Klebsiella pneumoniae with antibiofilm, non-toxic and non-hemolytic properties were then docked to MrkH, a transcriptional regulator of type 3 fimbriae involved in biofilm formation. Five of eight peptides bound more strongly than the native MrkH ligand when analyzed using HADDOCK and HPEPDOCK. Following the docking studies, our MD simulated that a Neuropeptide B (Peptide 3) bind strongly to the MrkH active sites. The discovery of putative AMPs that exceed the binding energies of the native ligand underscores the utility of the combined ML and molecular simulation strategies for discovering novel AMPs with antibiofilm properties.

Matched MeSH terms: Anti-Bacterial Agents/pharmacology
Bioassay-Guided Isolation and in Silico Study of Antibacterial Compounds From Petroleum Ether Extract of Peperomia blanda (Jacq.) Kunth

Al-Madhagi WM, Hashim NM, Awadh Ali NA, Taha H, Alhadi AA, Abdullah AA, et al.

J Chem Inf Model, 2019 05 28;59(5):1858-1872.
PMID: 31117526 DOI: 10.1021/acs.jcim.8b00969

Bioassay-guided isolation protocol was performed on petroleum ether extract of Peperomia blanda (Jacq.) Kunth using column chromatographic techniques. Five compounds were isolated and their structures were elucidated via one-dimensional (1D) and two-dimensional (2D) NMR, gas chromatography mass sectroscopy (GCMS), liquid chromatography mass spectroscopy (LCMS), and ultraviolet (UV) and infrared (IR) analyses. Dindygulerione E (a new compound), and two compounds isolated from P. blanda for the first time-namely, dindygulerione A and flavokawain A-are reported herein. Antimicrobial activity was screened against selected pathogenic microbes, and minimum inhibitory concentrations (MIC) were recorded within the range of 62-250 μg/mL. Assessment of the pharmacotherapeutic potential has also been done for the isolated compounds, using the Prediction of Activity spectra for Substances (PASS) software, and different activities of compounds were predicted. Molecular docking, molecular dynamics simulation and molecular mechanics/Poisson-Boltzmann Surface Area (MM-PBSA) calculations have proposed the binding affinity of these compounds toward methylthioadenosine phosphorylase enzyme, which may explain their inhibitory actions.

Matched MeSH terms: Anti-Bacterial Agents/pharmacology*
Fulltext Efficient Catalyst One-Pot Synthesis of 7-(Aryl)-10,10-dimethyl-10,11-dihydrochromeno[4,3-b]chromene-6,8(7H,9H)-dione Derivatives Complemented by Antibacterial Activity

Al-Majedy YK, Al-Amiery AA, Kadhum AA, Mohamad AB

Biomed Res Int, 2016;2016:5891703.
PMID: 27563671 DOI: 10.1155/2016/5891703

The problem of bacteria resistance to many known agents has inspired scientists and researchers to discover novel efficient antibacterial drugs. Three rapid, clean, and highly efficient methods were developed for one-pot synthesis of 7-(aryl)-10,10-dimethyl-10,11-dihydrochromeno[4,3-b]chromene-6,8(7H,9H)-dione derivatives. Three components are condensed in the synthesis, 4-hydroxycoumarin, 5,5-dimethyl-1,3-cyclohexanedione, and aromatic aldehydes, using tetrabutylammonium bromide (TBAB), diammonium hydrogen phosphate (DAHP), or ferric chloride (FeCl3), respectively. Each method has different reaction mechanisms according to the catalyst. The present methods have advantages, including one-pot synthesis, excellent yields, short reaction times, and easy isolation of product. All catalysts utilized in our study could be reused several times without losing their catalytic efficiency. All synthesized compounds were fully characterized and evaluated for their antibacterial activity.

Matched MeSH terms: Anti-Bacterial Agents/pharmacology
Supercritical fluid extraction of four aromatic herbs and assessment of the volatile compositions, bioactive compounds, antibacterial, and anti-biofilm activity

Al-Maqtari QA, Al-Ansi W, Mahdi AA, Al-Gheethi AAS, Mushtaq BS, Al-Adeeb A, et al.

Environ Sci Pollut Res Int, 2021 May;28(20):25479-25492.
PMID: 33462691 DOI: 10.1007/s11356-021-12346-6

Artemisia arborescens, Artemisia abyssinica, Pulicaria jaubertii, and Pulicaria petiolaris are fragrant herbs traditionally used in medication and as a food seasoning. To date, there are no studies on the use of supercritical fluids extraction with carbon dioxide (SFE-CO2) on these plants. This study evaluates and compares total phenolic content (TPC), antioxidant activity by DPPH• and ABTS•+, antibacterial, and anti-biofilm activities of SFE-CO2 extracts. Extraction was done by SFE-CO2 with 10% ethanol as a co-solvent. A. abyssinica extract had the highest extraction yield (8.9% ± 0.41). The GC/MS analysis of volatile compounds identified 307, 265, 213, and 201compounds in A. abyssinica, A. arborescens, P. jaubertii, and P. petiolaris, respectively. The P. jaubertii extract had the highest TPC (662.46 ± 50.93 mg gallic acid equivalent/g dry extract), antioxidant activity (58.98% ± 0.20), and antioxidant capacity (71.78 ± 1.84 mg Trolox equivalent/g dry extract). The A. abyssinica and P. jaubertii extracts had significantly higher antimicrobial activity and were more effective against Gram-positive bacteria. B. subtilis was the most sensitive bacterium. P. aeruginosa was the most resistant bacterium. P. jaubertii extract had the optimum MIC and MBC (0.4 mg/ml) against B. subtilis. All SFE-CO2 extracts were effective as an anti-biofilm formation for all tested bacteria at 1/2 MIC. Meanwhile, P. jaubertii and P. petiolaris extracts were effective anti-biofilm for most tested bacteria at 1/16 MIC. Overall, the results indicated that the SFE-CO2 extracts of these plants are good sources of TPC, antioxidants, and antibacterial, and they have promising applications in the industrial fields.

Matched MeSH terms: Anti-Bacterial Agents/pharmacology
Fulltext Molecular Analysis of Antibiotic Resistance Determinants and Plasmids in Malaysian Isolates of Multidrug Resistant Klebsiella pneumoniae

Al-Marzooq F, Mohd Yusof MY, Tay ST

PLoS One, 2015;10(7):e0133654.
PMID: 26203651 DOI: 10.1371/journal.pone.0133654

Infections caused by multidrug resistant Klebsiella pneumoniae have been increasingly reported in many parts of the world. A total of 93 Malaysian multidrug resistant K. pneumoniae isolated from patients attending to University of Malaya Medical Center, Kuala Lumpur, Malaysia from 2010-2012 were investigated for antibiotic resistance determinants including extended-spectrum beta-lactamases (ESBLs), aminoglycoside and trimethoprim/sulfamethoxazole resistance genes and plasmid replicons. CTX-M-15 (91.3%) was the predominant ESBL gene detected in this study. aacC2 gene (67.7%) was the most common gene detected in aminoglycoside-resistant isolates. Trimethoprim/sulfamethoxazole resistance (90.3%) was attributed to the presence of sul1 (53.8%) and dfrA (59.1%) genes in the isolates. Multiple plasmid replicons (1-4) were detected in 95.7% of the isolates. FIIK was the dominant replicon detected together with 13 other types of plasmid replicons. Conjugative plasmids (1-3 plasmids of ~3-100 kb) were obtained from 27 of 43 K. pneumoniae isolates. An ESBL gene (either CTX-M-15, CTX-M-3 or SHV-12) was detected from each transconjugant. Co-detection with at least one of other antibiotic resistance determinants [sul1, dfrA, aacC2, aac(6')-Ib, aac(6')-Ib-cr and qnrB] was noted in most conjugative plasmids. The transconjugants were resistant to multiple antibiotics including β-lactams, gentamicin and cotrimoxazole, but not ciprofloxacin. This is the first study describing the characterization of plasmids circulating in Malaysian multidrug resistant K. pneumoniae isolates. The results of this study suggest the diffusion of highly diverse plasmids with multiple antibiotic resistance determinants among the Malaysian isolates. Effective infection control measures and antibiotic stewardship programs should be adopted to limit the spread of the multidrug resistant bacteria in healthcare settings.

Matched MeSH terms: Anti-Bacterial Agents/pharmacology
Identification of a novel SHV-β-lactamase variant (SHV-144) in a Malaysian multidrug-resistant Klebsiella pneumoniae isolate

Al-Marzooq F, Yusof MY, Tay ST

Jpn J Infect Dis, 2013;66(6):555-7.
PMID: 24270152
Matched MeSH terms: Anti-Bacterial Agents/pharmacology
Emergence of Klebsiella pneumoniae producing dual carbapenemases (NDM-1 and OXA-232) and 16S rRNA methylase (armA) isolated from a Malaysian patient returning from India

Al-Marzooq F, Ngeow YF, Tay ST

Int J Antimicrob Agents, 2015 Apr;45(4):445-6.
PMID: 25631676 DOI: 10.1016/j.ijantimicag.2014.12.013
Matched MeSH terms: Anti-Bacterial Agents/pharmacology
Fulltext Chemical Composition and Antioxidant, Antimicrobial, and Anti-Inflammatory Properties of Origanum compactum Benth Essential Oils from Two Regions: In Vitro and In Vivo Evidence and In Silico Molecular Investigations

Al-Mijalli SH, Mrabti NN, Ouassou H, Sheikh RA, Assaggaf H, Bakrim S, et al.

Molecules, 2022 Oct 28;27(21).
PMID: 36364152 DOI: 10.3390/molecules27217329

The purposes of this investigatory study were to determine the chemical composition of the essential oils (EOs) of Origanum compactum from two Moroccan regions (Boulemane and Taounate), as well as the evaluation of their biological effects. Determining EOs' chemical composition was performed by a gas chromatography-mass spectrophotometer (GC-MS). The antioxidant activity of EOs was evaluated using free radical scavenging ability (DPPH method), fluorescence recovery after photobleaching (FRAP), and lipid peroxidation inhibition assays. The anti-inflammatory effect was assessed in vitro using the 5-lipoxygenase (5-LOX) inhibition test and in vivo using the carrageenan-induced paw edema model. Finally, the antibacterial effect was evaluated against several strains using the disk-diffusion assay and the micro-dilution method. The chemical constituent of O. compactum EO (OCEO) from the Boulemane zone is dominated by carvacrol (45.80%), thymol (18.86%), and α-pinene (13.43%). However, OCEO from the Taounate zone is rich in 3-carene (19.56%), thymol (12.98%), and o-cymene (11.16%). OCEO from Taounate showed higher antioxidant activity than EO from Boulemane. Nevertheless, EO from Boulemane considerably inhibited 5-LOX (IC50 = 0.68 ± 0.02 µg/mL) compared to EO from Taounate (IC50 = 1.33 ± 0.01 µg/mL). A similar result was obtained for tyrosinase inhibition with Boulemane EO and Taounate EO, which gave IC50s of 27.51 ± 0.03 μg/mL and 41.83 ± 0.01 μg/mL, respectively. The in vivo anti-inflammatory test showed promising effects; both EOs inhibit and reduce inflammation in mice. For antibacterial activity, both EOs were found to be significantly active against all strains tested in the disk-diffusion test, but O. compactum EO from the Boulemane region showed the highest activity. Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) for O. compactum EO from the Boulemane region ranged from 0.06 to 0.25% (v/v) and from 0.15 to 0.21% (v/v) for O. compactum from the Taounate region. The MBC/MIC index revealed that both EOs exhibited remarkable bactericidal effects.

Matched MeSH terms: Anti-Bacterial Agents/pharmacology
Fulltext Unveiling the volatile compounds and antibacterial mechanisms of action of Cupressus sempervirens L., against Bacillus subtilis and Pseudomonas aeruginosa

Al-Mijalli SH, El Hachlafi N, Jeddi M, Abdallah EM, Assaggaf H, Qasem A, et al.

Biomed Pharmacother, 2023 Nov;167:115609.
PMID: 37801906 DOI: 10.1016/j.biopha.2023.115609

Cupressus sempervirens is a known traditional plant used to manage various ailments, including cancer, inflammatory and infectious diseases. In this investigation, we aimed to explore the chemical profile of Cupressus sempervirens essential oil (CSEO) as well as their antibacterial mode of action. The volatile components were characterized using gas chromatography coupled to a mass spectrometer (GC-MS). The results revealed remarkable antibacterial properties of EO derived from C. sempervirens. GC-MS analysis indicated that C. sempervirens EO characterized by δ-3-carene (47.72%), D-limonene (5.44%), β-pinene (4.36%), β-myrcene (4.02%). The oil exhibited significant inhibitory effects against a range of bacteria, including Staphylococcus aureus ATCC 29213, Bacillus subtilis ATCC 13048, Bacillus cereus (Clinical isolate), Pseudomonas aeruginosa ATCC 27853, and Escherichia coli ATCC 25922. These inhibitory effects surpassed those of conventional antibiotics. Furthermore, the EO demonstrated low minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs), indicating its bactericidal nature (MBC/MIC < 4.0). Time-kill kinetics analysis showed that CSEO was particularly effective at 2 × MIC doses, rapidly reduced viable count of B. subtilis and P. aeruginosa within 8 h. This suggests that the oil acts quickly and efficiently. The cell membrane permeability test further demonstrated the impact of CSEO on the relative conductivity of B. subtilis and P. aeruginosa, both at 2 × MIC concentrations. These observations suggest that EO disrupts the bacterial membrane, thereby influencing their growth and viability. Additionally, the cell membrane integrity test indicated that the addition of CSEO to bacterial cultures resulted in the significant release of proteins from the bacterial cells. This suggests that EO affects the structural integrity of the bacterial cells. Furthermore, the anti-biofilm assay confirmed the efficacy of CSEO as a potent anti-biofilm agent. It demonstrated the oil's ability to inhibit quorum sensing, a crucial mechanism for biofilm formation, and its competitive performance compared to the tested antibiotics.

Matched MeSH terms: Anti-Bacterial Agents/pharmacology
Fulltext Enhanced Pharmaceutically Active Compounds Productivity from Streptomyces SUK 25: Optimization, Characterization, Mechanism and Techno-Economic Analysis

Al-Shaibani MM, Radin Mohamed RMS, Zin NM, Al-Gheethi A, Al-Sahari M, El Enshasy HA

Molecules, 2021 Apr 25;26(9).
PMID: 33923072 DOI: 10.3390/molecules26092510

The present research aimed to enhance the pharmaceutically active compounds' (PhACs') productivity from Streptomyces SUK 25 in submerged fermentation using response surface methodology (RSM) as a tool for optimization. Besides, the characteristics and mechanism of PhACs against methicillin-resistant Staphylococcus aureus were determined. Further, the techno-economic analysis of PhACs production was estimated. The independent factors include the following: incubation time, pH, temperature, shaker rotation speed, the concentration of glucose, mannitol, and asparagine, although the responses were the dry weight of crude extracts, minimum inhibitory concentration, and inhibition zone and were determined by RSM. The PhACs were characterized using GC-MS and FTIR, while the mechanism of action was determined using gene ontology extracted from DNA microarray data. The results revealed that the best operating parameters for the dry mass crude extracts production were 8.20 mg/L, the minimum inhibitory concentrations (MIC) value was 8.00 µg/mL, and an inhibition zone of 17.60 mm was determined after 12 days, pH 7, temperature 28 °C, shaker rotation speed 120 rpm, 1 g glucose /L, 3 g mannitol/L, and 0.5 g asparagine/L with R2 coefficient value of 0.70. The GC-MS and FTIR spectra confirmed the presence of 21 PhACs, and several functional groups were detected. The gene ontology revealed that 485 genes were upregulated and nine genes were downregulated. The specific and annual operation cost of the production of PhACs was U.S. Dollar (U.S.D) 48.61 per 100 mg compared to U.S.D 164.3/100 mg of the market price, indicating that it is economically cheaper than that at the market price.

Matched MeSH terms: Anti-Bacterial Agents/pharmacology*

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