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Fulltext Carbapenem resistance gene crisis in A. baumannii: a computational analysis

Zahra N, Zeshan B, Ishaq M

BMC Microbiol, 2022 Dec 03;22(1):290.
PMID: 36463105 DOI: 10.1186/s12866-022-02706-8

Acinetobacter baumannii (A. baumannii) is one of the members of ESKAPE bacteria which is considered multidrug resistant globally. The objective of this study is to determine the protein docking of different antibiotic resistance gene (ARGs) in A. baumannii. In silico analysis of antibiotic resistance genes against carbapenem are the blaOXA-51, blaOXA-23, blaOXA-58, blaOXA-24, blaOXA-143, NMD-1 and IMP-1 in A. baumannii. The doripenem, imipenem and meropenem were docked to blaOXA-51 and blaOXA-23 using PyRx. The top docking energy was -5.5 kcal/mol by imipenem and doripenem and meropenem showed a binding score of -5. 2 kcal/mol each and blaOXA-23 energy was -4.3 kcal/mol by imipenem and meropenem showed a binding score of -2.3 kcal/mol, while doripenem showed the binding score of -3.4 kcal/mol. Similarly, doripenem imipenem and meropenem were docked to blaOXA-58, IMP-1, Rec A and blaOXA-143, with docking energy was -8.8 kcal/mol by doripenem and meropenem each while imipenem showed a binding score of -4.2 kcal/mol and with IMP-1 demonstrated their binding energies. was -5.7 kcal/mol by meropenem and doripenem showed a binding score of -5.3 kcal/mol, while imipenem showed a binding score of -4.5 kcal/mol. And docking energy was -4.9 kcal/mol by imipenem and meropenem showed binding energy of -3.6 kcal/mol each while doripenem showed a binding score of -3.9 kcal/mol in RecA and with blaOXA-143 docking energy was -3.0 kcal/mol by imipenem and meropenem showed a binding score of -1.9 kcal/mol, while doripenem showed the binding score of -2.5 kcal/mol respectively. Doripenem, imipenem, and meropenem docking findings with blaOXA-24 confirmed their binding energies. Doripenem had the highest docking energy of -5.5 kcal/mol, meropenem had a binding score of -4.0 kcal/mol, and imipenem had a binding score of -3.9 kcal/mol. PyRx was used to dock the doripenem, imipenem, and meropenem to NMD-1. Docking energies for doripenem were all - 4.0 kcal/mol, whereas meropenem had docking energy of -3.3 kcal/mol and imipenem was -1.50 kcal/mol. To the best of our knowledge the underlying mechanism of phenotypic with genotypic resistance molecular docking regarding carbapenem resistance A. baumannii is unclear. Our molecular docking finds the possible protein targeting mechanism for carbapenem-resistant A.baumannii.
Biological and physical characterization of bacteriophage JHA against multidrug-resistant Acinetobacter baumannii

Ajmal H, Sharif Z, Zeshan B, Zahra N, Khan M

Pak J Pharm Sci, 2022 Sep;35(5):1327-1331.
PMID: 36451560

Due to the emergence of antibiotic resistance, bacteriophage therapy appears to be an ideal weapon to utilize against pathogenic bacteria. This study aimed to isolate, identify and characterize the lytic bacteriophage effective against the multidrug-resistant Acinetobacter baumannii clinical isolates. The isolated bacteriophage caused lysis by applying the double-layer agar technique on A. baumannii up to 99% in 18 hours of incubation at 37ºC. The bacterial growth reduction assay exhibited that JHA phage had high adsorption rates and could rapidly inhibit bacterial growth. The pH and thermal stability testing showed that JHA phage was stable in vast ranges of pH from 5 to 9 but its activity was highest at pH7 (1860000±1000 pfu/mL). It was stable in broad ranges of temperatures from 25ºC to 60ºC but the highest activity was found at 37ºC (1300000±30000 pfu/mL). One-step growth test results showed that it has a short latent period, strong lytic ability, high burst size and adsorption rates and was host specific. Scanning electron microscopy (SEM) of JHA phage demonstrated icosahedral heads and tailless particles. Transmission electron microscopy (TEM) revealed JHA phage belongs to Tectiviridae family. All the characteristics of JHA phage possess lytic activity against A. baumannii strains and exhibit novel candidates to use as an alternative competitor to antibiotics in controlling such infections.
Fulltext Plasma ferritin, C-reactive protein, and adenosine deaminase levels in tuberculous lymphadenitis and pleuritis and their role in monitoring treatment response

Nisa ZU, Zeshan B, Ambreen A, Mustafa T

BMC Infect Dis, 2024 Dec 02;24(1):1375.
PMID: 39623309 DOI: 10.1186/s12879-024-10228-z

BACKGROUND: We aimed to assess the plasma levels of ferritin, C-reactive protein (CRP), and adenosine deaminase (ADA) at baseline and their utility as biomarkers to monitor response to treatment in extrapulmonary tuberculosis (EPTB) patients.
METHODS: Prospective measurements of ferritin, CRP, and ADA were done in unstimulated plasma samples of 92 EPTB (49 TB lymphadenitis and 43 TB pleuritis) patients registered for anti-TB treatment. Blood samples were taken at the start, 2, and 6 months of treatment, plasma levels of ferritin and CRP were measured by the enzyme-linked immunosorbent assay and ADA levels by kinetic chemistry method at each time point. Data was analyzed using SPSS version 22. Non-parametric tests were used for paired analysis and two groups' comparison. Spearman's rank test was used for correlation analysis. A Chi-square test was used for categorical variables. A p-value
Fulltext Comparing the molecular evolution and recombination patterns of predominant PRRSV-2 lineages co-circulating in China

Zhang R, Li H, Xie H, Hou X, Zhou L, Cao A, et al.

Front Microbiol, 2024;15:1398470.
PMID: 38737413 DOI: 10.3389/fmicb.2024.1398470

Porcine reproductive and respiratory syndrome virus (PRRSV) poses widespread epidemics in swine herds, yet the drivers underlying lineage replacements/fitness dynamics remain unclear. To delineate the evolutionary trajectories of PRRSV-2 lineages prevalent in China, we performed a comprehensive longitudinal phylodynamic analysis of 822 viral sequences spanning 1991-2022. The objectives encompassed evaluating lineage dynamics, genetic diversity, recombination patterns and glycosylation profiles. A significant shift in the dominance of PRRSV-2 sub-lineages has been observed over the past 3 decades, transitioning from sub-lineage 8.7 to sub-lineage 1.8, followed by extensive diversification. The analysis revealed discordant recombination patterns between the two dominant viral sub-lineages 1.8 and 8.7, underscoring that modular genetic exchanges contribute significantly to their evolutionary shaping. Additionally, a strong association was found between recombination breakpoint locations and transcriptional regulatory sequences (TRSs). Glycosylation patterns also demonstrated considerable variability across sub-lineages and temporally, providing evidence for immune-driven viral evolution. Furthermore, we quantified different evolutionary rates across sub-lineages, with sub-lineage 1.8 uniquely displaying the highest nucleotide substitution rates. Taken together, these findings provide refined insight into the evolutionary mechanisms underpinning cyclic shifts in dominance among regionally circulating PRRSV sub-lineages.
Fulltext Green Synthesis and Characterization of Silver Nanoparticles Using Zingiber officinale Extracts to Investigate Their Antibacterial Potential

Ramzan M, Abusalah MAHA, Ahmed N, Yean CY, Zeshan B

Int J Nanomedicine, 2024;19:13319-13338.
PMID: 39679248 DOI: 10.2147/IJN.S475656

BACKGROUND AND PURPOSE: Antimicrobial resistance (AMR) has emerged as a significant global concern. To combat this growing threat, various strategies have been employed, including the use of plant extracts and the biosynthesis of nanoparticles (NPs). The current study was designed to evaluate the phytochemical analysis of ginger (Zingiber officinale) extracts, characterize the silver nanoparticles (AgNPs) and to see their antibacterial potentials against multi-drug resistant (MDR) bacterial strains.
METHODS: The extracts were prepared and initially assessed for their phytochemical composition and antibacterial activity. Then, AgNPs were synthesized from these extracts at room temperature, and various analytical techniques, including UV-visible spectroscopy, X-ray diffraction (XRD), ATIR-FTIR, zeta sizer, scanning electron microscopy (SEM), and energy-dispersive X-ray analysis (EDXA), were used to characterize the NPs. After confirmation of prepared NPs, they were subjected to their antibacterial activity.
RESULTS: HPLC analysis demonstrated the presence of eight phytoconstituents in organic ginger extracts. The absorption spectra of the silver suspension exhibited surface plasmon resonance peaks with maxima between 420 and 448 nm. Functional groups like C-H, N-H, OH, C-O-C, C=O, and C-O were identified in both the organic and aqueous extracts of Z. officinale, playing a key role in the formation of AgNPs, as characterized by ATR-FTIR analysis. Both ginger organic and aqueous extract synthesized AgNPs crystalline structure was shown in XRD analysis and the particle size distribution showed average diameter of 200.5 nm of AgNPs from aqueous extracts. Scanning Electron Microscopy displayed spherical structure and EDA results showed the percentage of elements in synthesized AgNPs using plant extracts. Most promising antibacterial activity was obtained against Escherichia coli ie 20.83±0.53 for 100 µg/mL.
CONCLUSION: The results of the current study showed that AgNPs synthesized from different ginger extracts have promising antibacterial properties and can be potential candidates for alternative treatment options for bacterial infections.
Novel cellular evidence of oviduct secretions in the Chinese soft-shelled turtle Pelodiscus sinensis

Waqas MY, Lisi H, Yang P, Ullah S, Zhang L, Zhang Q, et al.

J Exp Zool A Ecol Genet Physiol, 2015 Nov;323(9):655-65.
PMID: 26350585 DOI: 10.1002/jez.1957

The oviduct is the location of fertilization and sperm storage. We examined the ultrastructure of the oviduct epithelium and its glandular secretions in the isthmus, uterus and vagina of Chinese soft-shelled turtle Pelodiscus sinensis using light and transmission electron microscopy. The epithelium in these segments is lined with ciliated, secretory and other cells; the first two cell types span the entire epithelium, with secretory cells being predominant. The ciliated cells are characterized by the presence of a secretory vacuole that releases apocrine secretions into the lumen, whereas the secretory cells contain typical biphasic granules with both dark and light aspects. The third type of cells observed have wider proximal portion, abundant mitochondria, vacuoles, and narrow nuclei. The storage of spermatozoa is restricted to the isthmus, uterus, and vagina. In addition, the gland cells show prominent features, including the presence of granules of different shapes, sizes, and electron densities. The synthesis of these granules is described for the first time in this study. Mitochondria appear to play an important role in the formation of dense granules, the rough endoplasmic reticulum and microfilaments may also play a role in the maturation of these dense granules. After completing the maturation process, these granules are released into the lumen of the gland cells.
Fulltext The transcriptional characteristics of NADC34-like PRRSV in porcine alveolar macrophages

Wang P, Ma X, Zhang R, Zhao Y, Hu R, Luo C, et al.

Front Microbiol, 2022;13:1022481.
PMID: 36338035 DOI: 10.3389/fmicb.2022.1022481

The widespread and endemic circulation of porcine reproductive and respiratory syndrome virus (PRRSV) cause persistent financial losses to the swine industry worldwide. In 2017, NADC34-like PRRSV-2 emerged in northeastern China and spread rapidly. The dynamics analysis of immune perturbations associated with novel PRRSV lineage is still incomplete. This study performed a time-course transcriptome sequencing of NADC34-like PRRSV strain YC-2020-infected porcine alveolar macrophages (PAMs) and compared them with JXA1-infected PAMs. The results illustrated dramatic changes in the host's differentially expressed genes (DEGs) presented at different timepoints after PRRSV infection, and the expression profile of YC-2020 group is distinct from that of JXA1 group. Functional enrichment analysis showed that the expression of many inflammatory cytokines was up-regulated following YC-2020 infection but at a significantly lower magnitude than JXA1 group, in line with the trends for most interferon-stimulated genes (ISGs) and their regulators. Meanwhile, numerous components of histocompatibility complex (MHC) class II and phagosome presented a stronger transcription suppression after the YC-2020 infection. All results imply that YC-2020 may induce milder inflammatory responses, weaker antiviral processes, and more severe disturbance of antigen processing and presentation compared with HP-PRRSV. Additionally, LAPTM4A, GLMP, and LITAF, which were selected from weighted gene co-expression network analysis (WGCNA), could significantly inhibit PRRSV proliferation. This study provides fundamental data for understanding the biological characteristics of NADC34-like PRRSV and new insights into PRRSV evolution and prevention.
Fulltext A novel Pseudorabies virus vaccine developed using HDR-CRISPR/Cas9 induces strong humoral and cellular immune response in mice

Luo C, Wang Q, Guo R, Zhang J, Zhang J, Zhang R, et al.

Virus Res, 2022 Dec;322:198937.
PMID: 36174845 DOI: 10.1016/j.virusres.2022.198937

Outbreaks of Pseudorabies (PR) by numerous highly virulent and antigenic variant Pseudorabies virus (PRV) strains have been causing severe economic losses to the pig industry in China since 2011. However, current commercial vaccines are often unable to induce thorough protective immunity. In this study, a TK/gI/gE deleted recombinant PRV expressing GM-CSF was developed by using the HDR-CRISPR/Cas9 system. Here, a four-sgRNA along with the Cas9D10A targeting system was utilized for TK/gI/gE gene deletion and GM-CSF insertion. Our study showed that the four-sgRNA targeting system appeared to have higher knock-in efficiency for PRVs editing. The replication of the recombinant PRVs were slightly lower than that of the parental strain, but they appeared to have similar properties in terms of growth curves and plaque morphology. The mice vaccinated with the recombinant PRV expressing GM-CSF via intramuscular injection showed no obvious clinical symptoms, milder pathological lesions, and were completely protected against wild-type PRV challenge. When compared to the triple gene-deleted PRV, the gB antibodies and neutralizing antibody titers were improved and the immunized mice appeared to have lower viral load and higher mRNA levels of IL-2, IL-4, IL-6, and IFN-γ in spleens. Our study offers a novel approach for recombinant PRV construction, and the triple gene-deleted PRV expressing GM-CSF could serve as a promising vaccine candidate for PR control.
Lineage 1 PRRSVs Infection Induces Hemorrhagic Injury in Intestines of Piglets: Effects on Complement and Coagulation Cascades

Zhao Y, Wang R, Li W, Ren G, Zhang Y, Guo R, et al.

Microb Pathog, 2024 May 13.
PMID: 38750776 DOI: 10.1016/j.micpath.2024.106682

Porcine reproductive and respiratory syndrome virus (PRRSV) causes a highly transmissible disease of significant concern in the pig industry. Previous studies have demonstrated that the XM-2020 strain (a lineage 1.8 PRRSV IA/2012/NADC30) can induce special hemorrhagic injury in the small intestines. However, the specific mechanism underlying this injurious effect remains incompletely understood. In this study, we examined the pathogenic properties of XM-2020 and YC-2020 strains (a lineage 1.5 PRRSV IA/2014/NADC34) in piglets. Animal pathogenic tests revealed that with either Lineage 1 PRRSVs strains XM-2020 or YC-2020 demonstrated pronounced intestinal hemorrhage and suppression of peripheral immunological organs, comparing to JXA1 infection. Transcriptome analysis of diseased small intestines unveiled that PRRSV infection stimulated oxidative and inflammatory reactions. Remarkably, we also observed activation of the complement system alongside a notable down-regulation of complement and coagulation cascade pathways in the Lineage 1 PRRSVs infection group. Based on these findings, we propose that the primary mechanism driving the hemorrhagic injury of the small intestine caused by Lineage 1 PRRSVs is the suppression of complement and coagulation cascades resulting from immunosuppression. This discovery deepens our understanding of the pathogenicity of PRRSV in the small intestine and provides promising ways out for the development of innovative strategies aimed at controlling PRRSV.