EXPRESS: B-lymphocyte induced maturation protein-1 to inhibit inflammation and pyroptosis to alleviate sepsis injury.

Liver and lung tissue damage caused by sepsis still one of the causes of death. Blimp-1 has a protective role in inflammation-related disease. However, whether Blimp-1 can regulate cell pyroptosis and affect disease progression in sepsis is still unclear. Animal and cell models were established by cecal ligation and puncture (CLP) method and LPS-induced RAW 264.7 cells respectively, and the role of Blimp-1 in regulation inflammatory response and pyroptosis was verified. The changes of inflammation and pyroptosis in liver and lung tissues of septic mice were determined by the addition of TAK-242 (TLR4 inhibitor). Cell pyroptosis and the level of inflammation was detected after Blimp-1 knockdown and TAK-242 treatment in the cell model. The expression of Blimp-1 was continuously increased in a septic mice model. After treatment with TAK-242, the expression of Blimp-1, pyroptosis and inflammatory levels were reduced in mice. In LPS-induced cell model, cell injury by knockout Blimp-1 was increased, and cell activity was restored after TAK-242 intervention. Our study had shown that Blimp-1 could improve septic damage by regulating the level of cellular inflammation and pyroptosis in sepsis.

Identification of ISVlu1-derived translocatable units containing optrA and/or fexA genes generated by homologous or illegitimate recombination in Lactococcus garvieae of porcine origin.

The optrA gene encodes an ABC-F protein which confers cross-resistance to oxazolidinones and phenicols. Insertion sequence ISVlu1, a novel ISL3-family member, was recently reported to be involved in the transmission of optrA in Vagococcus lutrae. However, the role of ISVlu1 in mobilizing resistance genes has not yet fully explored. In this study, two complete and three truncated copies of ISVlu1 were found on plasmid pBN62-optrA from Lactococcus garvieae. Analysis of the genetic context showed that both optrA and the phenicols resistance gene fexA were flanked by the complete or truncated ISVlu1 copies. Moreover, three different-sized ISVlu1-based translocatable units (TUs) carrying optrA and/or fexA, were detected from pBN62-optrA. Sequence analysis revealed that the TU-optrA was generated by homologous recombination while TU-fexA and TU-optrA+fexA were the products of illegitimate recombinations. Importantly, conjugation assays confirmed that pBN62-optrA was able to successfully transfer into the recipient Enterococcus faecalis JH2-2. To our knowledge, this is the first report about an optrA-carrying plasmid in L. garvieae which could horizontally transfer into other species. More importantly, the ISVlu1-flanked genetic structures containing optrA and/or fexA were also observed in bacteria of different species, which underlines that ISVlu1 is highly active and plays a vital role in the transfer of some important resistance genes, such as optrA and fexA.

Synergistic effects of ceftazidime/avibactam combined with meropenem in a murine model of infection with KPC-producing Klebsiella pneumoniae.

OBJECTIVES: The emergence and expansion of carbapenem-resistant Klebsiella pneumoniae infections is a concern due to the lack of 'first-line' antibiotic treatment options. The ceftazidime/avibactam is an important clinical treatment for carbapenem-resistant K. pneumoniae infections but there is an increasing number of cases of treatment failure and drug resistance. Therefore, a potential solution is combination therapies that result in synergistic activity against K. pneumoniae carbapenemase: producing K. pneumoniae (KPC-Kp) isolates and preventing the emergence of KPC mutants resistant to ceftazidime/avibactam are needed in lieu of novel antibiotics. METHODS: To evaluate their synergistic activity, antibiotic combinations were tested against 26 KPC-Kp strains. Antibiotic resistance profiles, molecular characteristics and virulence genes were investigated by susceptibility testing and whole-genome sequencing. Antibiotic synergy was evaluated by in vitro chequerboard experiments, time-killing curves and dose-response assays. The mouse thigh model was used to confirm antibiotic combination activities in vivo. Additionally, antibiotic combinations were evaluated for their ability to prevent the emergence of ceftazidime/avibactam resistant mutations of blaKPC. RESULTS: The combination of ceftazidime/avibactam plus meropenem showed remarkable synergistic activity against 26 strains and restored susceptibility to both the partnering antibiotics. The significant therapeutic effect of ceftazidime/avibactam combined with meropenem was also confirmed in the mouse model and bacterial loads in the thigh muscle of the combination groups were significantly reduced. Furthermore, ceftazidime/avibactam plus meropenem showed significant activity in preventing the occurrence of resistance mutations. CONCLUSIONS: Our results indicated that the combination of ceftazidime/avibactam plus meropenem offers viable therapeutic alternatives in treating serious infections due to KPC-Kp.

SARS-CoV-2 NSP12 utilizes various host splicing factors for replication and splicing regulation.

The RNA-dependent RNA polymerase (RdRp) is a crucial element in the replication and transcription of RNA viruses. Although the RdRps of lethal human coronaviruses severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV) have been extensively studied, the molecular mechanism of the catalytic subunit NSP12, which is involved in pathogenesis, remains unclear. In this study, the biochemical and cell biological results demonstrate the interactions between SARS-CoV-2 NSP12 and seven host proteins, including three splicing factors (SLU7, PPIL3, and AKAP8). The entry efficacy of SARS-CoV-2 considerably decreased when SLU7 or PPIL3 was knocked out, indicating that abnormal splicing of the host genome was responsible for this occurrence. Furthermore, the polymerase activity and stability of SARS-CoV-2 RdRp were affected by the three splicing factors to varying degrees. In addition, NSP12 and its homologues from SARS-CoV and MERS-CoV suppressed the alternative splicing of cellular genes, which were influenced by the three splicing factors. Overall, our research illustrates that SARS-CoV-2 NSP12 can engage with various splicing factors, thereby impacting virus entry, replication, and gene splicing. This not only improves our understanding of how viruses cause diseases but also lays the foundation for the development of antiviral therapies.

Bacteriophage endolysin Ply113 as a potent antibacterial agent against polymicrobial biofilms formed by enterococci and Staphylococcus aureus.

Antibiotic resistance in Enterococcus faecium, Enterococcus faecalis, and Staphylococcus aureus remains a major public health concern worldwide. Furthermore, these microbes frequently co-exist in biofilm-associated infections, largely nullifying antibiotic-based therapy. Therefore, it is imperative to develop an efficient therapeutic strategy for combating infections caused by polymicrobial biofilms. In this study, we investigated the antibacterial and antibiofilm activity of the bacteriophage endolysin Ply113 in vitro. Ply113 exhibited high and rapid lytic activity against E. faecium, E. faecalis, and S. aureus, including vancomycin-resistant Enterococcus and methicillin-resistant S. aureus isolates. Transmission electron microscopy revealed that Ply113 treatment led to the detachment of bacterial cell walls and considerable cell lysis. Ply113 maintained stable lytic activity over a temperature range of 4-45°C, over a pH range of 5.0-8.0, and in the presence of 0-400 mM NaCl. Ply113 treatment effectively eliminated the mono-species biofilms formed by E. faecium, E. faecalis, and S. aureus in a dose-dependent manner. Ply113 was also able to eliminate the dual-species biofilms of E. faecium-S. aureus and E. faecalis-S. aureus. Additionally, Ply113 exerted potent antibacterial efficacy in vivo, distinctly decreasing the bacterial loads in a murine peritoneal septicemia model. Our findings suggest that the bacteriophage endolysin Ply113 is a promising antimicrobial agent for the treatment of polymicrobial infections.

Endopeptidase O promotes Streptococcus suis immune evasion by cleaving the host- defence peptide cathelicidins.

Streptococcus suis is a zoonotic Gram-positive bacterium that causes invasive infections such as sepsis and meningitis, threatening public health worldwide. For successful establishment of infection, the bacterium should subvert the innate effectors of immune defence, including the cathelicidin family of host-defence peptides that combat pathogenic bacteria by directly disrupting cell membranes and coordinating immune responses. Here, our study shows that an extracellular endopeptidase O (PepO) of S. suis contributes to assisting the bacterium to resist cathelicidin-mediated killing, as the deletion of the pepO gene makes S. suis more sensitive to the human cathelicidin LL-37, as well as its mouse equivalent, mCRAMP. This protease targets and cleaves both LL-37 and mCRAMP, degrading them into shorter peptides with only a few amino acids, thereby abrogating their ability to kill S. suis. By cleaving LL-37 and mCRAMP, PepO impairs their chemotactic properties for neutrophil migration and undermines their anti-apoptosis activity, which is required for prolonging neutrophil lifespan. Also, PepO inhibits the ability of LL-37 and mCRAMP to promote lysosome development in macrophages. Moreover, the loss of PepO attenuates organ injury and decreases bacterial burdens in a murine model of S. suis bacteraemia. Taken together, these data provide novel insights into the role of the intrinsic proteolytic characteristics of PepO in S. suis-host interaction. Our findings demonstrate that S. suis utilizes the PepO protease to cleave cathelicidins, which is an immunosuppressive strategy adopted by this bacterium to facilitate pathogenesis.

Characterization of an optrA-harbouring unconventional circularizable structure located on a novel ICESa2603 family-like integrative and conjugative element ICESsuHN38 in Streptococcus suis.

OBJECTIVES: To identify the novel genetic elements involved in the horizontal transfer of the oxazolidinone/phenicol resistance gene optrA in Streptococcus suis. METHODS: Whole-genome DNA of the optrA-positive isolate S. suis HN38 was subjected to WGS via both Illumina HiSeq and Oxford Nanopore platforms. MICs of several antimicrobial agents (erythromycin, linezolid, chloramphenicol, florfenicol, rifampicin and tetracycline) were determined by broth microdilution. PCR assays were performed to identify the circular forms of the novel integrative and conjugative element (ICE) ICESsuHN38, but also the unconventional circularizable structure (UCS) excised from this ICE. The transferability of ICESsuHN38 was evaluated by conjugation assays. RESULTS: S. suis isolate HN38 harboured the oxazolidinone/phenicol resistance gene optrA. The optrA gene was flanked by two copies of erm(B) genes in the same orientation, located on a novel ICESa2603 family-like ICE, designated ICESsuHN38. PCR assays revealed that a novel UCS carrying the optrA and one copy of erm(B) could be excised from ICESsuHN38. Conjugation assays confirmed that ICESsuHN38 was able to successfully transfer into the recipient strain S. suis BAA. CONCLUSIONS: In this work, a novel optrA-carrying mobile genetic element, a UCS, was identified in S. suis. The optrA gene was flanked by copies of erm(B) and its location on the novel ICESsuHN38 will aid its horizontal dissemination.

Bactericidal synergism between phage endolysin Ply2660 and cathelicidin LL-37 against vancomycin-resistant Enterococcus faecalis biofilms.

Antibiotic resistance and the ability to form biofilms of Enterococcus faecalis have compromised the choice of therapeutic options, which triggered the search for new therapeutic strategies, such as the use of phage endolysins and antimicrobial peptides. However, few studies have addressed the synergistic relationship between these two promising options. Here, we investigated the combination of the phage endolysin Ply2660 and the antimicrobial peptide LL-37 to target drug-resistant biofilm-producing E. faecalis. In vitro bactericidal assays were used to demonstrate the efficacy of the Ply2660-LL-37 combination against E. faecalis. Larger reductions in viable cell counts were observed when Ply2660 and LL-37 were applied together than after individual treatment with either substance. Transmission electron microscopy revealed that the Ply2660-LL-37 combination could lead to severe cell lysis of E. faecalis. The mode of action of the Ply2660-LL-37 combination against E. faecalis was that Ply2660 degrades cell wall peptidoglycan, and subsequently, LL-37 destroys the cytoplasmic membrane. Furthermore, Ply2660 and LL-37 act synergistically to inhibit the biofilm formation of E. faecalis. The Ply2660-LL-37 combination also showed a synergistic effect for the treatment of established biofilm, as biofilm killing with this combination was superior to each substance alone. In a murine peritoneal septicemia model, the Ply2660-LL-37 combination distinctly suppressed the dissemination of E. faecalis isolates and attenuated organ injury, being more effective than each treatment alone. Altogether, our findings indicate that the combination of a phage endolysin and an antimicrobial peptide may be a potential antimicrobial strategy for combating E. faecalis.

Cajanin stilbene acid: A direct inhibitor of colistin resistance protein MCR-1 that restores the efficacy of polymyxin B against resistant Gram-negative bacteria.

BACKGROUND: The resistance of Gram-negative bacteria to polymyxin B, caused by the plasmid-mediated colistin resistance gene mcr-1, which encodes a phosphoethanolamine transferase (MCR-1), is a serious threat to global public health. Therefore, it is urgent to find new drugs that can effectively alleviate polymyxin B resistance. Through the screening of 78 natural compounds, we found that cajanin stilbene acid (CSA) can significantly restore the susceptibility of polymyxin B to mcr-1 positive Escherichia coli (E. coli). PURPOSE: In this study, we tried to evaluate the ability of CSA to restore the susceptibility of polymyxin B towards the E. coli, and explore the mechanism of sensitivity recovery. STUDY DESIGN AND METHODS: Checkerboard MICs, time-killing curves, scanning electron microscope, lethal and semi-lethal models of infection in mice were used to assess the ability of CSA to restore the susceptibility of polymyxyn to E. coli. The interaction between CSA and MCR-1 was evaluated using surface plasmon resonance (SPR), and molecular docking experiments. RESULTS: Here, we find that CSA, a potential direct inhibitor of MCR-1, effectively restores the sensitivity of E. coli to polymyxin B. CSA can restore the sensitivity of polymyxin B to drug-resistant E. coli, and the MIC value can be reduced to 1 µg/ml. The time killing curve and scanning electron microscopy results also showed that CSA can effectively restore polymyxin B sensitivity. In vivo experiments showed that the simultaneous use of CSA and polymyxin B can effectively reduce the infection of drug-resistant E. coli in mice. SPR and molecular docking experiments confirmed that CSA strongly bound to MCR-1. The 17-carbonyl oxygen and 12- and 18­hydroxyl oxygens of CSA were the key sites binding to MCR-1. CONCLUSION: CSA is able to significantly restore the sensitivity of polymyxin B to E. coli in vivo and in vitro. CSA inhibits the enzymatic activity of the MCR-1 protein by binding to key amino acids at the active center of the MCR-1 protein.

Integrative and conjugative elements in streptococci can act as vectors for plasmids and translocatable units integrated via IS1216E.

Mobile genetic elements (MGEs), such as integrative and conjugative elements (ICEs), plasmids and translocatable units (TUs), are important drivers for the spread of antibiotic resistance. Although ICEs have been reported to support the spread of plasmids among different bacteria, their role in mobilizing resistance plasmids and TUs has not yet been fully explored. In this study, a novel TU bearing optrA, a novel non-conjugative plasmid p5303-cfrD carrying cfr(D) and a new member of the ICESa2603 family, ICESg5301 were identified in streptococci. Polymerase chain reaction (PCR) assays revealed that three different types of cointegrates can be formed by IS1216E-mediated cointegration between the three different MGEs, including ICESg5301::p5303-cfrD::TU, ICESg5301::p5303-cfrD, and ICESg5301::TU. Conjugation assays showed that ICEs carrying p5303-cfrD and/or TU successfully transferred into recipient strains, thereby confirming that ICEs can serve as vectors for other non-conjugative MGEs, such as TUs and p5303-cfrD. As neither the TU nor plasmid p5303-cfrD can spread on their own between different bacteria, their integration into an ICE via IS1216E-mediated cointegrate formation not only increases the plasticity of ICEs, but also furthers the dissemination of plasmids and TUs carrying oxazolidinone resistance genes.

Integrated bioinformatic analyses investigate macrophage-M1-related biomarkers and tuberculosis therapeutic drugs.

Tuberculosis (TB) is a common infectious disease linked to host genetics and the innate immune response. It is vital to investigate new molecular mechanisms and efficient biomarkers for Tuberculosis because the pathophysiology of the disease is still unclear, and there aren't any precise diagnostic tools. This study downloaded three blood datasets from the GEO database, two of which (GSE19435 and 83456) were used to build a weighted gene co-expression network for searching hub genes associated with macrophage M1 by the CIBERSORT and WGCNA algorithms. Furthermore, 994 differentially expressed genes (DEGs) were extracted from healthy and TB samples, four of which were associated with macrophage M1, naming RTP4, CXCL10, CD38, and IFI44. They were confirmed as upregulation in TB samples by external dataset validation (GSE34608) and quantitative real-time PCR analysis (qRT-PCR). CMap was used to predict potential therapeutic compounds for tuberculosis using 300 differentially expressed genes (150 downregulated and 150 upregulated genes), and six small molecules (RWJ-21757, phenamil, benzanthrone, TG-101348, metyrapone, and WT-161) with a higher confidence value were extracted. We used in-depth bioinformatics analysis to investigate significant macrophage M1-related genes and promising anti-Tuberculosis therapeutic compounds. However, more clinical trials were necessary to determine their effect on Tuberculosis.

A CRISPR/Cas12a-assisted rapid detection platform by biosensing the apxIVA of Actinobacillus pleuropneumoniae.

Actinobacillus pleuropneumoniae is an important respiratory pig pathogen that causes substantial losses in the worldwide swine industry. Chronic or subclinical infection with no apparent clinical symptoms poses a challenge for preventing transmission between herds. Rapid diagnostics is important for the control of epidemic diseases. In this study, we formulated an A. pleuropneumoniae species-specific apxIVA-based CRISPR/Cas12a-assisted rapid detection platform (Card) that combines recombinase polymerase amplification (RPA) of target DNA and subsequent Cas12a ssDNase activation. Card has a detection limit of 10 CFUs of A. pleuropneumoniae, and there is no cross-reactivity with other common swine pathogens. The detection process can be completed in 1 h, and there was 100% agreement between the conventional apxIVA-based PCR and Card in detecting A. pleuropneumoniae in lung samples. Microplate fluorescence readout enables high-throughput use in diagnostic laboratories, and naked eye and lateral flow test readouts enable use at the point of care. We conclude that Card is a versatile, rapid, accurate molecular diagnostic platform suitable for use in both laboratory and low-resource settings.

Characterization of an MDR Lactobacillus salivarius isolate harbouring the phenicol-oxazolidinone-tetracycline resistance gene poxtA.

OBJECTIVES: To characterize the oxazolidinone resistance gene poxtA in a Lactobacillus salivarius isolate of pig origin. METHODS: L. salivarius isolate BNS11 was investigated for the presence of mobile oxazolidinone resistance genes by PCR. Antimicrobial susceptibility testing was performed by broth microdilution. Transfer experiments were conducted to assess horizontal transferability of the gene poxtA. WGS was carried out using a combination of Oxford Nanopore MinION/Illumina HiSeq platforms. The presence of translocatable units (TUs) carrying resistance genes was studied by PCR assays and subsequent sequence analysis. RESULTS: L. salivarius isolate BNS11 was positive for poxtA. WGS showed that it harboured two gene copies each of the poxtA and the fexB genes, which were located on the broad-host-range Inc18 plasmid pBNS11-37kb and in the chromosomal DNA, respectively. The plasmid-borne poxtA gene together with the genes fexB, vat(E) and erm(C) were located in an MDR region on plasmid pBNS11-37kb. Analysis of the genetic context showed that an approx. 11 kb poxtA-fexB fragment was integrated into the chromosomal DNA and two novel IS elements ISLasa1 and ISLasa2 were identified in this inserted fragment. PCR assays revealed that five different IS1216E-based TUs carrying the resistance genes poxtA, fexB, vat(E) or erm(C) were formed. CONCLUSIONS: To the best of our knowledge, this is the first report of the transferable oxazolidinone resistance gene poxtA in the genus Lactobacillus. In addition, the presence of IS1216E-based TUs will contribute to the persistence and accelerate the dissemination of resistance genes, including poxtA.

Characterization of the novel optrA-carrying pseudo-compound transposon Tn7363 and an Inc18 plasmid carrying cfr(D) in Vagococcus lutrae.

OBJECTIVES: To investigate the genetic context and transferability of the oxazolidinone resistance genes cfr(D) and optrA in a porcine Vagococcus lutrae isolate. METHODS: V. lutrae isolate BN31 was screened for the presence of known oxazolidinone resistance genes via PCR assays. Conjugation experiments were carried out to assess horizontal transferability of resistance genes. WGS was performed using a combination of Nanopore MinION and Illumina HiSeq platforms. Detection of a translocatable unit (TU) was conducted by PCR. RESULTS: V. lutrae isolate BN31 harboured the oxazolidinone resistance genes cfr(D) and optrA. The optrA gene, together with the phenicol resistance gene fexA, was located on a novel pseudo-compound transposon, designated Tn7363. Tn7363 was bounded by two copies of the new insertion sequence ISVlu1, which represented a new member of the ISL3 family. A TU, comprising one copy of ISVlu1 and the segment between the two IS elements including the optrA gene, was detected. The cfr(D) gene and an erm(B) gene were identified on the broad-host-range Inc18 plasmid pBN31-cfrD, a pAMß1-like plasmid. Similar to plasmid pAMß1, plasmid pBN31-cfrD was conjugative. CONCLUSIONS: To the best of our knowledge, we report the first identification of the cfr(D) and optrA in Vagococcus. Two novel oxazolidinone resistance gene-carrying mobile genetic elements, Tn7363 and pBN31-cfrD, were identified in V. lutrae BN31. Considering their transmission potential, attention should be paid to the risk of transfer of the optrA and cfr(D) genes from V. lutrae to clinically more important bacterial pathogens.

Characterization of a novel RepA_N-family plasmid harbouring the phenicol-oxazolidinone resistance gene optrA in Enterococcus faecalis ST16 high-risk clone of goat origin.

The occurrence and dissemination of linezolid-resistant Gram-positive bacteria among food-producing animals poses severe threats to public health. To date, information about the emergence of the oxazolidinone resistance gene optrA in isolates from goats is scare. In this study, the optrA-positive multiresistant E. faecalis strain SY-1 was isolated from a goat in China. E. faecalis strain SY-1 displayed a multidrug resistance profile for most of antimicrobial agents tested, including linezolid and tedizolid. MLST analysis showed that E. faecalis strain SY-1 belonged to the high-risk clone ST16. Whole genome sequencing analysis revealed that the optrA gene together with several other resistance genes was located on a novel RepA_N-family plasmid pSY-1-optrA. Detailed sequence analysis indicated that pSY-1-optrA exhibited a mosaic structure that may be the result of recombination events. In addition, a mobile bacitracin resistance operon bcrABDR was identified on plasmid pSY-1-optrA. In conclusion, this is, to our knowledge, the first report of the optrA gene in the high-risk clone E. faecalis ST16 of goat origin. Active surveillance of optrA-positive E. faecalis high-risk clones in food-producing animals is urgently warranted.

Genomic Insight into the Antimicrobial Resistance of Streptococcus Suis - Six Countries, 2011-2019.

WHAT IS ALREADY KNOWN ON THIS TOPIC?: Streptococcus suis (S. suis) is a zoonotic pathogen causing disease in humans and animals, and the emergence of its increased resistance to antimicrobial agents has become a significant challenge in many countries. WHAT IS ADDED BY THIS REPORT?: Using whole genome sequencing data to accurately predict antimicrobial resistance determinants, it was found that the prevalence of antimicrobial resistance genes was higher in the pig isolates of S. suis than in the human isolates and that the prevalence of these genes varied with serotype. WHAT ARE THE IMPLICATIONS FOR PUBLIC HEALTH PRACTICE?: The data regarding S. suis antimicrobial resistance will help guide rational drug use in the clinic to better protect the health of humans and animals.

Selecting Hub Genes and Predicting Target Genes of microRNAs in Tuberculosis via the Bioinformatics Analysis.

Tuberculosis (TB) is the world's most prevalently infectious disease. Molecular mechanisms behind tuberculosis remain unknown. microRNA (miRNA) is involved in a wide variety of diseases. To validate the significant genes and miRNAs in the current sample, two messenger RNA (mRNA) expression profile datasets and three miRNA expression profile datasets were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed (DE) genes (DEGs) and miRNAs (DE miRNAs) between healthy and TB patients were filtered out. Enrichment analysis was executed, and a protein-protein interaction (PPI) network was developed to understand the enrich pathways and hub genes of TB. Additionally, the target genes of miRNA were predicted and overlapping target genes were identified. We studied a total of 181 DEGs (135 downregulated and 46 upregulated genes) and two DE miRNAs (2 downregulated miRNAs) from two gene profile datasets and three miRNA profile datasets, respectively. 10 hub genes were defined based on high degree of connectivity. A PPI network's top module was constructed. The 23 DEGs identified have a significant relationship with miRNAs. 25 critically significant Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were discovered. The detailed study revealed that, in tuberculosis, the DE miRNA and DEGs form an interaction network. The identification of novel target genes and main pathways would aid with our understanding of miRNA's function in tuberculosis progression.