Molecular Basis of Pulmonary Disease

Farver, Carol; Zander, Dani S.

doi:10.1016/b978-0-12-374419-7.00018-4

Cited by 8 publications

(7 citation statements)

References 252 publications

(272 reference statements)

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“…Skin integrity was preserved in mice treated with 43Hf after the infection, and vancomycin (Van)-treated infected skin showed minimal inflammation (Figure 8c). The MRSA infection caused severe alveolar destruction and interstitium thickening in the lung tissue of the vehicle group, as S. aureus usually spread to the lung through the blood from skin, 48 while treatment with 43Hf and Van obviously reduced the changes (Figure S14). H&E stained sections of heart, liver, kidney, and spleen revealed no histopathological changes (Figure S14).…”

Section: ■ Resultsmentioning

confidence: 99%

Discovery of Novel Peptidomimetic Boronate ClpP Inhibitors with Noncanonical Enzyme Mechanism as Potent Virulence Blockers in Vitro and in Vivo

Zhou

et al. 2020

J. Med. Chem.

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Caseinolytic protease P (ClpP) is considered as a promising target for the treatment of Staphylococcus aureus infections. In an unbiased screen of 2632 molecules, a peptidomimetic boronate, MLN9708, was found to be a potent suppressor of SaClpP function. A time-saving and cost-efficient strategy integrating in silico position scanning, multistep miniaturized synthesis, and bioactivity testing was deployed for optimization of this hit compound and led to fast exploration of structure−activity relationships. Five of 150 compounds from the miniaturized synthesis exhibited improved inhibitory activity. Compound 43Hf was the most active inhibitor and showed reversible covalent binding to SaClpP while did not destabilize the tetradecameric structure of SaClpP. The crystal structure of 43Hf-SaClpP complex provided mechanistic insight into the covalent binding mode of peptidomimetic boronate and SaClpP. Furthermore, 43Hf could bind endogenous ClpP in S. aureus cells and exhibited significant efficacy in attenuating S. aureus virulence in vitro and in vivo.

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Section: ■ Resultsmentioning

confidence: 99%

Discovery of Novel Peptidomimetic Boronate ClpP Inhibitors with Noncanonical Enzyme Mechanism as Potent Virulence Blockers in Vitro and in Vivo

Zhou

et al. 2020

J. Med. Chem.

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“…It is known that staphylococcal pneumonia is caused by S. aureus , which usually spreads to the lung through the blood from other infected sites, most often the skin. Though a common community pathogen, it is found twice as frequently in pneumonias occurring in hospitalized patients [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

Microbiology and Clinical Outcome of Hospital-Acquired Respiratory Infections in an Italian Teaching Hospital: A Retrospective Study

et al. 2022

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The burden, microbial etiology and clinical impact of hospital-acquired respiratory infections (HARIs) were determined at an Italian teaching hospital over a 12-month period. For this purpose, overall ordinary hospitalizations ≥ 2 days of subjects over 18 years old with discharge from 1 January 2018 to 31 December 2018 were examined by cross-referencing demographic and clinical data from hospital discharge forms with microbiological data from the computer system of the Microbiology Unit. We identified 329 individuals with HARIs (96 females and 233 males; median age 70 years, range 18–93), who represented ¼ of the total hospital-acquired infections (HAIs) in the period. The inpatient setting was medical and surgical in similar proportions (169 vs. 160, respectively) and the mean hospital stay was 38.9 ± 33.6 days. One hundred and forty patients (42.6 % of the total sample) were suffering from one or more chronic diseases. A total of 581 microorganisms (82 antibiotic-resistant and 499 non-resistant) were detected in HARI patients. The most common isolated species were Staphylococcus aureus (16.7%), Klebsiella pneumoniae (13.3%), Pseudomonas spp. (12.6%) and Acinetobacter baumannii (10.5%), followed by Enterobacter spp. (5.3%), Escherichia coli (5.2%) and Enterococcus spp. (4.8%). One hundred and sixty-seven individuals (49.0% of the total) had polymicrobial infections. One hundred thirty-one patients (39.8% of the total) underwent endotracheal intubation and mechanical ventilation and 62.6% of them died, compared to 17.7% of the non-intubated patients. Multivariable analysis confirmed a positive correlation between death and increased age (p = 0.05), surgical MDC (p = 0.007), number of microorganisms over the sample mean (p = 0.001), the presence of chronic diseases (p = 0.046), and intubation and mechanical ventilation (p < 0.0001). A positive correlation between intubation and antibiotic-resistant organisms (p = 0.003) was also found. HARIs are still a major public health problem and require constant surveillance due to their severe clinical outcome.

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“…It is a member of polyketide antibiotic family and possesses high activity against Gram-positive bacteria, including Clostridium perfringens . Antimicrobial activity of zincophorin has been extended to Streptococcus pneumonia lately [ 195 ], the leading cause of bacterial pneumonia [ 196 ]. In general, minimal inhibitory concentration (MIC) and minimal biofilm inhibitory concentration (MBIC) of zincophorin for three reference strains and four clinical isolates of S. pneumoniae are lower than for daptomycin [ 196 ] (a relatively new lipopeptide antibiotic used for the treatment of gram-positive life-threatening infections) [ 197 ].…”

Section: Antibacterial Zn(ii) Ionophoresmentioning

confidence: 99%

“…Antimicrobial activity of zincophorin has been extended to Streptococcus pneumonia lately [195], the leading cause of bacterial pneumonia [196]. In general, minimal inhibitory concentration (MIC) and minimal biofilm inhibitory concentration (MBIC) of zincophorin for three reference strains and four clinical isolates of S. pneumoniae are lower than for daptomycin [196] (a relatively new lipopeptide antibiotic used for the treatment of gram-positive life-threatening infections) [197]. It is worth mentioning that zincophorin losses its antimicrobial activity upon esterification of its carboxylate group.…”

Section: Zincophorinmentioning

confidence: 99%

Zinc(II)—The Overlooked Éminence Grise of Chloroquine’s Fight against COVID-19?

et al. 2020

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Zn(II) is an inhibitor of SARS-CoV-2′s RNA-dependent RNA polymerase, and chloroquine and hydroxychloroquine are Zn(II) ionophores–this statement gives a curious mind a lot to think about. We show results of the first clinical trials on chloroquine (CQ) and hydroxychloroquine (HCQ) in the treatment of COVID-19, as well as earlier reports on the anticoronaviral properties of these two compounds and of Zn(II) itself. Other FDA-approved Zn(II) ionophores are given a decent amount of attention and are thought of as possible COVID-19 therapeutics.

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Molecular Basis of Pulmonary Disease

Cited by 8 publications

References 252 publications

Discovery of Novel Peptidomimetic Boronate ClpP Inhibitors with Noncanonical Enzyme Mechanism as Potent Virulence Blockers in Vitro and in Vivo

Discovery of Novel Peptidomimetic Boronate ClpP Inhibitors with Noncanonical Enzyme Mechanism as Potent Virulence Blockers in Vitro and in Vivo

Microbiology and Clinical Outcome of Hospital-Acquired Respiratory Infections in an Italian Teaching Hospital: A Retrospective Study

Zinc(II)—The Overlooked Éminence Grise of Chloroquine’s Fight against COVID-19?

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