Agent Of Pneumonia Research Articles

Toll-like receptor 10 has a role in human macrophage response against Streptococcus pneumoniae.

Toll-like receptors (TLRs) are evolutionarily conserved pathogen-associated molecular pattern recognition receptors, and play a critical role in early response against invading pathogens. Even though TLRs have been widely studied, very little is known about the expression and function of TLR10. Till date, neither any data are available on expression of TLR10 in human lungs nor there is any information on function of TLR10 in macrophages. Streptococcus pneumoniae are Gram-positive, alpha-hemolytic, and major causative agent of pneumonia, ear infections, sinus infections, and meningitis. We examined the role of TLR10 in innate immune response to S. pneumoniae infection in U937 cell line-derived human macrophages. We found a significant increase in TLR10 mRNA and protein expression in S. pneumoniae challenged macrophages. TLR10 knockdown resulted in significant reduction of IL-1β, IL-8, IL-17, and TNF-α but not IL-10 expression in infected macrophages. TLR10 knockdown in macrophages reduced nuclear translocation of NF-κB during S. pneumoniae challenge but did not affect the phagocytosis of the bacteria. Taken together, we report the first data on TLR10's role in macrophage response against S. pneumoniae.

Artificial stem cells mediated inflammation-tropic delivery of antiviral drugs for pneumonia treatment

BackgroundCytomegalovirus (CMV) pneumonia is a major cause of morbidity and mortality in immunodeficiency individuals, including transplant recipients and Acquired Immune Deficiency Syndrome patients. Antiviral drugs ganciclovir (GCV) and phosphonoformate (PFA) are first-line agents for pneumonia caused by herpesvirus infection. However, the therapy suffers from various limitations such as low efficiency, drug resistance, toxicity, and lack of specificity.MethodsThe antiviral drugs GCV and PFA were loaded into the pH-responsive nanoparticles fabricated by poly(lactic-co-glycolic acid) (PLGA) and 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), and further coated with cell membranes derived from bone marrow mesenchymal stem cells to form artificial stem cells, namely MPDGP. We evaluated the viral suppression effects of MPDGP in vitro and in vivo.ResultsMPDGP showed significant inflammation tropism and efficient suppression of viral replication and virus infection-associated inflammation in the CMV-induced pneumonia model. The synergistic effects of the combination of viral DNA elongation inhibitor GCV and viral DNA polymerase inhibitor PFA on suppressing the inflammation efficiently.ConclusionThe present study develops a novel therapeutic intervention using artificial stem cells to deliver antiviral drugs at inflammatory sites, which shows great potential for the targeted treatment of pneumonia. To our best knowledge, we are the first to fabricate this kind of artificial stem cell to deliver antiviral drugs for pneumonia treatment.Graphical

Nocardia otitidiscaviarum as Possible Etiologic Agent of Non-resolving Pneumonia

Nocardia otitidiscaviarum as Possible Etiologic Agent of Non-resolving Pneumonia

Loop-Mediated Isothermal Amplification Coupled With Nanoparticle-Based Biosensor: A Rapid and Sensitive Method to Detect Mycoplasma pneumoniae.

Mycoplasma pneumoniae (MP), the causative agent of MP pneumonia (MPP), has posed a substantial burden to public health owing to a lack of rapid and effective diagnostic methods. Here, we designed a loop-mediated isothermal amplification (LAMP)-based assay, termed LAMP, combined with a nanoparticle-based lateral flow biosensor (LAMP-LFB) for rapid and sensitive diagnosis of MP.-LAMP-LFB included a set of six primers targeting the community-acquired respiratory distress syndrome (CARDS) toxin gene and was performed optimally at 63°C for only 30 min. The resulting LAMP products could be visually indicated by LFB within 2 min, thus the whole process could be accomplished within an hour. MP-LAMP-LFB’s sensitivity was 50 fg per reaction, which was in complete accordance with these results obtained from real-time turbidity and visual detection reagent (VDR). MP-LAMP-LFB had no cross-reactivity with other pathogens that had similar clinical presentations. Our assay was further validated using 100 nasopharyngeal swab samples collected from children suspected of MPP, and the result was compared with the real-time PCR method. With a positive rate of 50%, the data indicated that MP-LAMP-LFB is a sensitive test for MP detection in clinical settings. Collectively, the MP-LAMP-LFB assay targeting the CARDS toxin gene was a rapid, highly sensitive, and specific test that could be widely applied in point-of-care settings and basic medical facilities in rural areas.

Chemotherapeutic Strategies with Valnemulin, Tilmicosin, and Tulathromycin to Control Mycoplasma hyopneumoniae Infection in Pigs.

Mycoplasma hyopneumoniae is the primary agent of Swine Enzootic Pneumonia (SEP). Vaccines reduce the clinical manifestation of the disease but do not prevent infection. The present study aimed to evaluate the use of antimicrobial drugs to minimize the impact of M. hyopneumoniae. For this, 32 pregnant female pigs and their litters were selected and then followed from birth to slaughter. The study involved three experimental groups that received metaphylactic treatment with different protocols involving tilmicosin, valnemulin, tulathromycin, and a control group to compare the effect of treatments against M. hyopneumoniae infection throughout the phases. Performance data were recorded, and the piglets were evaluated for the occurrence of cough. Nasal swab and blood collection was conducted periodically to detect M. hyopneumoniae shedding and anti-M. hyopneumoniae IgG, respectively. At slaughter, the lungs of animals from all groups were evaluated, and samples were collected for histopathological examination and qPCR for M. hyopneumoniae detection. All protocols promoted a reduction in consolidation lung lesions when compared to the control group. Individuals treated with valnemulin showed increased performance results, lower mortality, and low bacterial load in the lung. The results are promising and may indicate an alternative in the strategic control of M. hyopneumoniae infection in pigs.

Evaluation of the Efficacy and Safety of Initial Empirical Antibiotic Therapy for Community-Acquired Pneumonia in Middle-Aged People

β-lactam antibiotics, including cephalosporins, are the drugs of choice for empirical antibiotic therapy (ABT) in patients with community-acquired pneumonia. Unreasonable and irrational use of antibiotics leads to an increased risk of adverse reactions, contributes to the growth of antibiotic resistance.The aim of the study was to analyse data on the efficacy and safety of initial empirical ABT using cephalosporins for community-acquired pneumonia in middle-aged patients of multidisciplinary hospitals in Moscow.Materials and methods: the authors analysed 177 archived medical records of the patients admitted to three multidisciplinary hospitals (I.V. Davydovsky City Clinical Hospital, City Clinical Hospital 52 and City Clinical Hospital 4) in Moscow from 2017 to 2019 and prescribed mono- and/or combination therapy including a cephalosporin antibiotic as a starting therapy for community-acquired pneumonia. The initial ABT was considered effective if a patient’s body temperature normalised within 48–72 h following initiation of treatment and safe if no adverse reactions developed during the period of inpatient treatment.Results: the combination of ceftriaxone and azithromycin was the most frequently prescribed ABT regimen; its effectiveness was 71.9%. Ceftriaxone monotherapy was the second in frequency of prescription; its effectiveness amounted to 77.2%. The third regimen included cefotaxime and azithromycin and was effective in 70% of cases. The patients who needed a change in initial ABT had a significantly higher incidence of developing severe community-acquired pneumonia and complications. The study results indicate that the structure of comorbidity did not affect the effectiveness of initial empirical ABT. Streptococcus pneumoniae was found to be the most common causative agent of community-acquired pneumonia in the studied population (44.8% of cases). Only 13% of the patients faced adverse reactions associated with the use of antibiotics as part of the initial empirical ABT; the most common were leukopenia and diarrhoea.Сonclusions: the results of the study indicate the feasibility of mono- and/or combination ABT including a cephalosporin antibiotic as a starting empirical therapy for community-acquired pneumonia due to its effectiveness and favourable safety profile.

Carbapenem-Resistant Klebsiella pneumoniae Among Patients with Ventilator-Associated Pneumonia: Evaluation of Antibiotic Combinations and Susceptibility to New Antibiotics.

BackgroundCarbapenemase-producing Gram-negative bacteria, particularly Klebsiella pneumoniae (K. pneumoniae), are at the forefront of the list of causative agents of ventilator-associated pneumonia (VAP). The treatment options for such infections are limited, and various antimicrobial combinations have been suggested as alternatives in clinical practice. New antibiotics, such as ceftazidime/avibactam, ceftolozane/tazobactam and cefiderocol, have shown advantages in both in vitro and clinical studies.PurposeTo evaluate the in vitro effect of meropenem–ciprofloxacin and meropenem–colistin combinations on carbapenem-resistant (CR) K. pneumoniae VAP isolates and to determine their susceptibility to new antibiotics.MethodsSeventy-three K. pneumoniae isolates from 176 endotracheal samples from VAP cases were studied. Antibiotic susceptibility testing and phenotypic detection of extended-spectrum β lactamase (ESBL) and carbapenemase production were done. CR K. pneumoniae isolates were tested for the five predominant carbapenemase genes (blaKPC, blaOXA-48, blaNDM, blaVIM, and blaIMP). In vitro evaluation of meropenem–ciprofloxacin and meropenem–colistin combinations was done by MIC test strips. Susceptibility to new antibiotics was tested by disk diffusion method.ResultsSixty-three (86.3%) of the isolates were ESBL producers and 52 (71.2%) were carbapenem resistant. BlaNDM was the most prevalent carbapenemase gene (50%), followed by blaOXA-48, (36.5%) then blaKPC in (11.5%). BlaVIM and blaIMP were not detected. Meropenem–ciprofloxacin combination showed indifferent effect on all isolates, while meropenem–colistin combination showed 25% synergism, 15.4% addition and 59.6% indifference. All (100%) CR K. pneumoniae isolates were resistant to ceftolozane/tazobactam and 79% were resistant to ceftazidime/avibactam, while 96% were sensitive to cefiderocol.ConclusionA high rate of carbapenem resistance exists among VAP K. pneumoniae isolates. Meropenem–colistin combination and cefiderocol appear to be potential treatment options for infections caused by CR K. pneumoniae. Resistance to the tested new β-lactam/β-lactamase inhibitors was high, signifying a major threat.

Detection of causative agents of bacterial pneumonia in hospitalized hajj and umrah cases by multiplex real-time polymerase chain reaction.

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is commonly detected in pneumonia patients who travel from the Middle East regions. Besides MERS-CoV, many other pathogenic agents cause pneumonia. Detection of such organisms must be done swiftly, especially in case of the negative MERS-CoV samples. The aim of this study was to identify the pathogenic agents that might account for bacterial pneumonia, from Hajj and Umrah pneumonia cases. We conducted a cross-sectional study, 38 pneumonia clinical samples from suffering of Hajj and Umrah in 2017 with negative MERS-CoV were selected. The laboratory testing was done at National Reference Laboratory in Jakarta and performed by multiplex real-time PCR using a FTD respiratory pathogens. Haemophilus influenzae (26.4%) was the most frequent bacteria detected. Other causative agents of bacterial pneumonia identified were Moraxella catarrhalis (20.8%), Klebsiella pneumoniae (13.2%), Streptococcus pneumoniae (9.4%), and Staphylococcus aureus (5.7%). From 38 samples showed that 25 (65.79%) samples were positive with bacteria, including five samples with coinfection. The coinfection were combinations among S. aureus and S. pneumoniae (1/20), S. pneumoniae and K. pneumoniae (1/20), S. pneumoniae and M. catarrhalis (2/20), S. pneumoniae and H. influenzae (2/20), K. pneumoniae and H. influenzae (5/20), and M. catarrhalis and H. influenzae (5/20). Haemophilus influenzae is the most recurrent bacteria to be identified in samples of pneumonia of hajj and umrah cases.

Microflora of sputum and autopsy material of patients with COVID-19.

The rapid spread of a new coronavirus infection in the country actualizes the conduct of bacteriological studies of clinical material obtained from the respiratory tract of patients with COVID-19. During the experiments, 230 sputum samples and 260 autopsy lung samples from patients with COVID-19 were analyzed. 946 high-risk strains were isolated and identified by MALDI-ToF mass spectrometry on a Microflex LT instrument (Bruker®). According to the results of bacteriological cultures of sputum, a predominance of gram-positive ones was revealed, amounting to 50.5% (222 strains) of the total number of isolated pathogens. However, falling into this group is manifested by natural representatives of the microflora of the human mucous membranes from the genera Streptococcus, Rothia and Lactobacillus (109 strains in total), which can be manifested by the detection of improper sputum collection, causing contamination by the substance of intense salivation and nasopharyngeal discharge. In turn, the "classic" gram-positive causative agents of pneumonia were detected much less frequently: S. aureus in 5 cases, S. pneumoniae in 6 patients. The causative agents in the order Enterobacterales are represented by 42 strains, among which the most likely species are K.pneumoniae (27 strains). In the group of non-fermenting gram-negative bacteria, A. baumanii (29 strains) prevailed, and P. aeruginosa was also identified in 2 cases. When analyzing the results of a microbiological study of autopsy material (lungs) of patients with COVID-19, significant differences in the qualitative and quantitative composition of the microflora were revealed, compared with sputum. In the group of gram-positive bacteria, 15 strains of the natural microflora of the mucous membranes were identified, while sensitive species dominated among gram-negative pathogens: K. pneumoniae (102 strains), A. baumanii (75 strains), P. aeruginosa (11 strains). Regular microbiological monitoring is essential for antibiotic therapy and prevention of secondary bacterial infection. In the event of a fatal outcome, the results of microbiological analysis of autopsy material can determine the cause of death of the patient.

Minilungs from Human Embryonic Stem Cells to Study the Interaction of Streptococcus pneumoniae with the Respiratory Tract.

ABSTRACTThe new generation of organoids derived from human pluripotent stem cells holds a promising strategy for modeling host-bacteria interaction studies. Organoids recapitulate the composition, diversity of cell types, and, to some extent, the functional features of the native organ. We generated lung bud organoids derived from human embryonic stem cells to study the interaction of Streptococcus pneumoniae (pneumococcus) with the alveolar epithelium. Invasive pneumococcal disease is an important health problem that may occur as a result of the spread of pneumococcus from the lower respiratory tract to sterile sites. We show here an efficient experimental approach to model the main events of the pneumococcal infection that occur in the human lung, exploring bacterial adherence to the epithelium and internalization and triggering an innate response that includes the interaction with surfactant and the expression of representative cytokines and chemokines. Thus, this model, based on human minilungs, can be used to study pneumococcal virulence factors and the pathogenesis of different serotypes, and it will allow therapeutic interventions in a reliable human context.IMPORTANCE Streptococcus pneumoniae is responsible for high morbidity and mortalities rates worldwide, affecting mainly children and adults older than 65 years. Pneumococcus is also the most common etiologic agent of bacterial pneumonia and nonepidemic meningitis, and it is a frequent cause of bacterial sepsis. Although the introduction of pneumococcal vaccines has decreased the burden of pneumococcal disease, the rise of antibiotic-resistant strains and nonvaccine types by serotype replacement is worrisome. To study the biology of pneumococcus and to establish a reliable human model for pneumococcal pathogenesis, we generated human minilungs from embryonic stem cells. The results show that these organoids can be used to model some events occurring during the interaction of pneumococcus with the lung, such as adherence, internalization, and the initial alveolar innate response. This model also represents a great alternative for studying virulence factors involved in pneumonia, drug screening, and other therapeutic interventions.

Antimicrobial Activity Assay of Liposomal Lipopolysaccharide Extracted from Escherichia coli.

Escherichia coli(E. coli) is a bacterial bacillus known to be negative for the gram dye, and it is part of the normal flora inside the human body. The current study aimed to investigate the possibility of using lipopolysaccharides (LPS) as an antimicrobial agent. A total of 30 isolates of E. coli were collected from 100 specimens of urine isolated from patients with recurrent urinary tract infections (UTIs) referring to Al-Sadr Teaching Hospital. The samples were cultured on identification media; thereafter, they were diagnosed according to the phenotypic form, biochemical tests, and finally by VITK-2. The results of the prevalence of E. coli isolates illustrated that from 30 isolates of E. coli which were collected from 100 urine specimens, 14 (46.6%), 6 (20%), and 10 (33.3%) cases belonged to the urinary tract infections, kidney stones, and urinary catheter samples, respectively. The isolates displayed multiple drug resistance (MDR) to most of the antibiotics used in the study. Therefore, the lipopolysaccharide extracted from E. coli was used as an antimicrobial agent. The recorded data obtained from the polymerase chain reaction (PCR) for WaaA, WaaC, wamB, and wabG genes demonstrated that the isolates possessed biosynthesis genes for LPS. The results indicated that LPS at concentrations of 150, 250, and 500 μg/ml has as an anti-growth agent for Klebsiella pneumonia, Proteus mirabilis, Salmonella typhi, Pseudomonas aeruginosa, Bacillus subtilis, Staph aureus, and candida albicans. The highest inhibitory effect was observed on K. pneumonia, P. mirabilis, S. typhi, B. subtilis, and C. albicans, as compared to the control antimicrobials agents (Amoxicillin, Nystatin). The LPS loaded on liposome nanoparticles can open new horizons in medicine by its inclusion in the manufacture of broad-spectrum antibiotics.

Glenthmycins A-M: Macrocyclic Spirotetronate Polyketide Antibacterials from the Australian Pasture Plant-Derived Streptomyces sp. CMB-PB041.

Chemical investigation of Australian pasture plant-derived Streptomyces sp. CMB-PB041, supported by miniaturized cultivation profiling and molecular network analysis, led to the isolation and characterization of 13 new macrocyclic spirotetronates, glenthmycins A-M (1-13), with structures assigned by detailed spectroscopic analysis, chemical degradation and derivatization, and mechanistic and biosynthetic considerations. Hydrolysis of glenthmycin B (2) yielded the aglycone 14, whose structure and absolute configuration were secured by X-ray analysis, along with the unexpected amino sugar residues glenthose lactams A (15) and B (16), with Mosher analysis of 15 facilitating assignment of absolute configurations of the amino sugar. While the glenthmycins proved to be acid stable, treatment of isomeric glenthmycins (i.e., 3, 6, and 8) with base catalyzed rapid intramolecular trans-esterification to regio-isomeric mixtures (i.e., 3 + 6 + 8). Exposure of 5 to base achieved the same intramolecular trans-esterification and was instrumental in detecting and tentatively identifying two additional minor co-metabolites, glenthmycins N (19) and O (20). A structure-activity relationship analysis carried out on 1-13 and the semisynthetic analogues 14 and 21-26 revealed a promising Gram +ve antibacterial pharmacophore, effective against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE), but with no detectable cytotoxicity to eukaryotic cells (i.e., fungal and human carcinoma). Of particular note, the semisynthetic analogue glenthmycin K 9-valerate (26) was unique among glenthmycins in potently inhibiting growth of the full panel of Gram +ve pathogens (IC50 0.2-1.6 μM). We conclude with an observation that any future evaluation of the antibacterial potential of glenthmycins and related macrocyclic spirotetronates may do well to include important soil-derived Gram +ve pathogens, such as Bacillus anthrax, Clostridium botulinum, and Rhodococcus equi, the causative agents of anthrax, botulism, and livestock pneumonia.

Causative Agents of Ventilator-Associated Pneumonia and Resistance to Antibiotics in COVID-19 Patients: A Systematic Review

Patients with coronavirus disease 2019 (COVID-19) have an increased risk of ventilator-associated pneumonia (VAP). This systematic review updates information on the causative agents of VAP and resistance to antibiotics in COVID-19 patients. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed/MEDLINE, and LILACS databases from December 2019 to December 2021. Studies that described the frequency of causative pathogens associated with VAP and their antibiotic resistance patterns in critically ill COVID-19 adult patients were included. The Newcastle-Ottawa Quality Assessment Scale was used for critical appraisal. The data are presented according to the number or proportions reported in the studies. A total of 25 articles were included, involving 2766 VAP cases in COVID-19 patients (range 5–550 VAP cases). Most of the studies included were carried out in France (32%), Italy (20%), Spain (12%) and the United States (8%). Gram-negative bacteria were the most frequent causative pathogens of VAP (range of incidences in studies: P. aeruginosa 7.5–72.5%, K. pneumoniae 6.9–43.7%, E. cloacae 1.6–20% and A. baumannii 1.2–20%). S. aureus was the most frequent Gram-positive pathogen, with a range of incidence of 3.3–57.9%. The median incidence of Aspergillus spp. was 6.4%. Few studies have recorded susceptibility patterns among Gram-negative causative pathogens and have mainly reported extended-spectrum beta-lactamase (ESBL), AmpC, and carbapenem resistance. The median frequency of methicillin resistance among S. aureus isolates was 44.4%. Our study provides the first comprehensive description of the causative agents and antibiotic resistance in COVID-19 patients with VAP. Gram-negative bacteria were the most common pathogens causing VAP. Data on antibiotic resistance patterns in the published medical literature are limited, as well as information about VAP from low- and middle-income countries.

Neutrophil Recruitment in Pneumococcal Pneumonia.

Streptococcus pneumoniae (Spn) is the primary agent of community-acquired pneumonia. Neutrophils are innate immune cells that are essential for bacterial clearance during pneumococcal pneumonia but can also do harm to host tissue. Neutrophil migration in pneumococcal pneumonia is therefore a major determinant of host disease outcomes. During Spn infection, detection of the bacterium leads to an increase in proinflammatory signals and subsequent expression of integrins and ligands on both the neutrophil as well as endothelial and epithelial cells. These integrins and ligands mediate the tethering and migration of the neutrophil from the bloodstream to the site of infection. A gradient of host-derived and bacterial-derived chemoattractants contribute to targeted movement of neutrophils. During pneumococcal pneumonia, neutrophils are rapidly recruited to the pulmonary space, but studies show that some of the canonical neutrophil migratory machinery is dispensable. Investigation of neutrophil migration is necessary for us to understand the dynamics of pneumococcal infection. Here, we summarize what is known about the pathways that lead to migration of the neutrophil from the capillaries to the lung during pneumococcal infection.

Seroprevalence of Mycoplasma hyopneumoniae in sows fifteen years after implementation of a control programme for enzootic pneumonia in Switzerland

Mycoplasma hyopneumoniae is the etiological agent of enzootic pneumonia (EP), an economically important chronic respiratory disease in pigs. M. hyopneumoniae impacts the mucociliary clearance system by disrupting the cilia and modulates the immune response, resulting in intermittent dry non-productive cough. For progressive control of EP in Switzerland, a corresponding programme was fully implemented in 2004. It is based on total depopulation strategies of affected fattening farms as well as partial depopulation in breeding farms. Surveillance of EP status in Switzerland is mainly based on real-time PCR of nasal swabs from coughing animals or suspicious lungs and thereby sporadic cases are still observed every year. In order to obtain information on the seroprevalence, serum samples of 5021 sows from 968 farms collected in 2018 at eight different slaughterhouses were analyzed for the presence of M. hyopneumoniae-specific antibodies using a commercial ELISA kit. The overall seroprevalence was low with 0.98% of sows testing positive and these seropositive animals could be allocated to 3.92% of farms tested. Most seropositive farms presented weakly positive singleton reactors and only one farm showed several strongly seropositive animals. In conclusion, the serological status mirrors the successful progressive control of M. hyopneumoniae in the Swiss domestic pig population over the years. The current study underlines the added value of serological testing in the surveillance of EP in a country with low prevalence and confirms the sustained benefit of strategic control programmes.

Unusual Lipid Components of Legionella gormanii Membranes.

Legionella spp. cause Legionnaires’ disease with pneumonia as the predominant clinical symptom. L. gormanii is the second most prevalent causative agent of community-acquired pneumonia after L. pneumophila. The study aimed to characterize the lipidome of L. gormanii membranes and the importance of these analyses in bacterial chemotaxonomy. Lipidomic analyses based on ultra-high performance liquid chromatography-mass spectrometry allowed the detection of individual molecular species of a wide range of L. gormanii membrane lipids contained in the outer (OM) and inner membranes (IM). The lipid profile comprised glycerolipids (triglycerides, diglycerides), phospholipids (phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, cardiolipin), and sphingolipids (ceramides, hexosylceramides). The most abundant lipid fraction in the IM and OM were phospholipids. The lipidomic analysis showed that two independent phosphatidylcholine (PC) synthesis pathways operating in L. gormanii: the PE-methylation (PmtA) pathway and the PC synthase (Pcs) pathway. Comparison of the molecular profile of PC species contained in the lipids of L. gormanii membranes cultured on the medium, with and without exogenous choline, showed quantitative differences in the PC pool. An unusual feature of the L. gormanii lipids was the presence of ceramides and hexosylceramides, which are typical components of eukaryotic cells and a very small group of bacteria. To the best of our knowledge, this is the first report of the occurrence of ceramides in Legionella bacteria.

Neumonía vírica. Neumonía en la COVID-19

Viruses are becoming more and more important as etiological agents of pneumonia, mainly due to improvements in diagnostic techniques. At present, they account for approximately one-third of community-acquired pneumonia cases. They tend to occur in children and elderly patients, causing anything from mild cases to severe cases which require intubation and intensive care. The main causative agents include rhinovirus, influenza virus A or B, metapneumovirus, respiratory syncytial virus, parainfluenza virus, coronavirus, or adenovirus. Infection produced by SARS-CoV-2, the cause of the current COVID-19 pandemic, which has had devastating consequences, is proof of the vital importance of viral pneumonia. This is the main subject of this update. Drawing on the abundant information available, which has been continuously evolving since the beginning of the pandemic, this section will review the main characteristics of the virus, its pathophysiology, and its clinical manifestations as well as the main diagnostic and treatment methods.

Inhalation of MSC-EVs is a noninvasive strategy for ameliorating acute lung injury.

Mesenchymal stem cell-derived small extracellular vesicles (MSC-EVs) are promising nanotherapeutic agent for pneumonia (bacterial origin, COVID-19), but the optimal administration route and potential mechanisms of action remain poorly understood. This study compared the administration of MSC-EVs via inhalation and tail vein injection for the treatment of acute lung injury (ALI) and determined the host-derived mechanisms that may contribute to the therapeutic effects of MSC-EVs in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells (macrophage cell line) and animal models. Luminex liquid chip and hematoxylin and eosin (HE) staining revealed that, compared with the vehicle control, inhaled MSC-EVs outperformed those injected via the tail vein, by reducing the expression of pro-inflammatory cytokines, increasing the expression of anti-inflammatory cytokine, and decreasing pathological scores in ALI. MSC-EV administration promoted the polarization of macrophages towards a M2 phenotype in vitro and in vivo (via inhalation). RNA sequencing revealed that immune and redox mediators, including TLR4, Arg1, and HO-1, were associated with the activity MSC-EVs against ALI mice. Western blotting and immunofluorescence revealed that correlative inflammatory and oxidative mediators were involved in the therapeutic effects of MSC-EVs in LPS-stimulated cells and mice. Moreover, variable expression of Nrf2 was observed following treatment with MSC-EVs in cell and animal models, and knockdown of Nrf2 attenuated the anti-inflammatory and antioxidant activities of MSC-EVs in LPS-stimulated macrophages. Together, these data suggest that inhalation of MSC-EVs as a noninvasive strategy for attenuation of ALI, and the adaptive regulation of Nrf2 may contribute to their anti-inflammatory and anti-oxidant activity in mice.

MIP From Legionella pneumophila Influences the Phagocytosis and Chemotaxis of RAW264.7 Macrophages by Regulating the lncRNA GAS5/miR-21/SOCS6 Axis.

BackgroundThe intracellular pathogen Legionella pneumophila (L. pneumophila) is a causative agent of pneumonia and does great harm to human health. These bacteria are phagocytosed by alveolar macrophages and survive to replicate within the macrophages. Despite macrophage infectivity potentiator (MIP) protein serving as an essential virulence factor during the invasion process of L. pneumophila, the regulatory mechanism of MIP protein in the process of bacterial infection to host cells is not yet completely understood. This research thus aims to explore the interaction between MIP and macrophage phagocytosis.MethodsThrough the experiment of the co-culture of RAW264.7 macrophages with different concentrations of MIP, the chemotactic activity of macrophages was detected and the phagocytosis was determined by a neutral red uptake assay. The expression of long noncoding RNA (lncRNA) GAS5, microRNA-21 (miR-21), and suppressor of cytokine signaling (SOCS)6 was determined by qRT-PCR. Target genes were detected by dual luciferase assay.ResultsMIP could reduce the phagocytosis and improve the chemotaxis of RAW264.7 macrophages. The expression of both lncRNA GAS5 and SOCS6 was increased whereas the expression of miR-21 was decreased when macrophages were treated with MIP. Dual luciferase assay revealed that lncRNA GAS5 could interact with miR-21, and SOCS6 served as the target of miR-21. After GAS5 overexpression, the phagocytosis of RAW264.7 treated with MIP was increased whereas the chemotaxis was decreased. In contrast, the opposite results were found in RAW264.7 following GAS5 interference.ConclusionsThe present results revealed that MIP could influence RAW264.7 macrophages on phagocytic and chemotactic activities through the axis of lncRNA GAS5/miR-21/SOCS6.

Current guidelines for the selection of an antibacterial drug in children with community-acquired pneumonia

The COVID-19 pandemic has affected the incidence of acute respiratory infections in the modern world. Despite the growing etiological significance of viruses in the structure of infectious diseases, the importance of bacterial pathogens in the development of respiratory pathology remains. The risk of unreasonable prescription of antibacterial drugs increases. The irrational use of antibacterial drugs has affected the spread of microorganisms with high resistance to antibiotics. The article presents current knowledge on the role of the most common pathogens of community-acquired pneumonia in children, data concerning the S. pneumoniae strain with reduced sensitivity and resistance to penicillin, macrolides. Information about isolates of S. Pneumoniae with decreased susceptibility to third-generation parenteral cephalosporins (cefotaxime and ceftriaxone) have appeared. The number of β-lactamase-producing strains of H. influenzae resistant to unprotected aminopenicillins is rising. The main steps of the diagnostic process of community-acquired pneumonia approved in the clinical guidelines for community-acquired pneumonia in children in 2022, which were adopted by the Russian Ministry of Health, are considered. This document sets out clear algorithms for diagnosing and selecting antibacterial therapy in children on an outpatient basis. Algorithms for selecting initial antibacterial therapy in outpatient settings are also proposed. In most cases, S. pneumoniae is a causative agent of community-acquired pneumonia in children, which defines the selection of an initial antibacterial drug. According to the clinical guidelines, oral amoxicillin at a standard dose of 45–55 mg/kg/day given in 2–3 divided doses is such a drug for children aged 3 months and older. Particular attention is paid to amoxicillin in the form of dispersible tablets.