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Article ; Online: Epidemiology and drug susceptibility of nontuberculous mycobacteria (NTM) in Italy in 2016-2020.

Giannoni, Federico / Lanni, Alessio / Iacobino, Angelo / Fattorini, Lanfranco

Annali dell'Istituto superiore di sanita

2023 Volume 59, Issue 2, Page(s) 132–138

Abstract: Introduction: Nontuberculous mycobacteria (NTM) are environmental mycobacteria which may cause pulmonary and extrapulmonary diseases. These organisms are difficult to treat due to their intrinsic drug-resistance. In Italy, no major nationwide study on ... ...

Abstract	Introduction: Nontuberculous mycobacteria (NTM) are environmental mycobacteria which may cause pulmonary and extrapulmonary diseases. These organisms are difficult to treat due to their intrinsic drug-resistance. In Italy, no major nationwide study on NTM epidemiology and drug susceptibility was performed. Methods: Data on the epidemiology of 7,469 NTM clinical isolates identified in Italy in 2016-2020 and on the minimum inhibitory concentrations (MICs) of 1,506 of these strains were analysed. Results: Overall, 63 species were identified in 42 hospital laboratories located in 16 out of 20 regions, with Mycobacterium avium complex (MAC) being the most frequently isolated, followed by M. gordonae, M. xenopi, M. abscessus. The MICs of 12 drugs for MAC, M. xenopi, M. kansasii, M. abscessus, M. fortuitum and M. chelonae were interpreted for clinical significance (susceptible, intermediate, resistant) based on the guidelines published by the Clinical and Laboratory Standards Institute in November 2018. Conclusions: Our data are in line with other nationwide studies and may be of value for further update of microbiological and clinical guidelines.
MeSH term(s)	Humans ; Nontuberculous Mycobacteria ; Mycobacterium Infections, Nontuberculous/epidemiology ; Mycobacterium Infections, Nontuberculous/microbiology ; Microbial Sensitivity Tests ; Italy/epidemiology
Language	English
Publishing date	2023-02-17
Publishing country	Italy
Document type	Journal Article
ZDB-ID	950344-4
ISSN	2384-8553 ; 0021-2571
ISSN (online)	2384-8553
ISSN	0021-2571
DOI	10.4415/ANN_23_02_06
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Eradication of Drug-Tolerant

Lanni, Alessio / Iacobino, Angelo / Fattorini, Lanfranco / Giannoni, Federico

Microorganisms

2023 Volume 11, Issue 6

Abstract: The lungs of tuberculosis (TB) patients contain a spectrum of granulomatous lesions, ranging from solid and well-vascularized cellular granulomas to avascular caseous granulomas. In solid granulomas, current therapy kills actively replicating (AR) ... ...

Abstract	The lungs of tuberculosis (TB) patients contain a spectrum of granulomatous lesions, ranging from solid and well-vascularized cellular granulomas to avascular caseous granulomas. In solid granulomas, current therapy kills actively replicating (AR) intracellular bacilli, while in low-vascularized caseous granulomas the low-oxygen tension stimulates aerobic and microaerophilic AR bacilli to transit into non-replicating (NR), drug-tolerant and extracellular stages. These stages, which do not have genetic mutations and are often referred to as persisters, are difficult to eradicate due to low drug penetration inside the caseum and mycobacterial cell walls. The sputum of TB patients also contains viable bacilli called differentially detectable (DD) cells that, unlike persisters, grow in liquid, but not in solid media. This review provides a comprehensive update on drug combinations killing in vitro AR and drug-tolerant bacilli (persisters and DD cells), and sterilizing
Language	English
Publishing date	2023-06-06
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms11061511
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Article: Activity of Drug Combinations against Mycobacterium abscessus Grown in Aerobic and Hypoxic Conditions

Lanni, Alessio / Borroni, Emanuele / Iacobino, Angelo / Russo, Cristina / Gentile, Leonarda / Fattorini, Lanfranco / Giannoni, Federico

Microorganisms. 2022 July 14, v. 10, no. 7

2022

Abstract: Infections caused by Mycobacterium abscessus (Mab), an environmental non-tuberculous mycobacterium, are difficult to eradicate from patients with pulmonary diseases such as cystic fibrosis and bronchiectasis even after years of antibiotic treatments. In ... ...

Abstract	Infections caused by Mycobacterium abscessus (Mab), an environmental non-tuberculous mycobacterium, are difficult to eradicate from patients with pulmonary diseases such as cystic fibrosis and bronchiectasis even after years of antibiotic treatments. In these people, the low oxygen pressure in mucus and biofilm may restrict Mab growth from actively replicating aerobic (A) to non-replicating hypoxic (H) stages, which are known to be extremely drug-tolerant. After the exposure of Mab A and H cells to drugs, killing was monitored by measuring colony-forming units (CFU) and regrowth in liquid medium (MGIT 960) of 1-day-old A cells (A1) and 5-day-old H cells (H5). Mab killing was defined as a lack of regrowth of drug-exposed cells in MGIT tubes after >50 days of incubation. Out of 18 drugs tested, 14-day treatments with bedaquiline-amikacin (BDQ-AMK)-containing three-drug combinations were very active against A1 + H5 cells. However, drug-tolerant cells (persisters) were not killed, as shown by CFU curves with typical bimodal trends. Instead, 56-day treatments with the nitrocompounds containing combinations BDQ-AMK-rifabutin-clarithromycin-nimorazole and BDQ-AMK-rifabutin-clarithromycin-metronidazole-colistin killed all A1 + H5 Mab cells in 42 and 56 days, respectively, as shown by lack of regrowth in agar and MGIT medium. Overall, these data indicated that Mab persisters may be killed by appropriate drug combinations.
Keywords	Mycobacterium abscessus ; agar ; antibiotics ; biofilm ; cystic fibrosis ; liquids ; mucus ; oxygen ; people ; regrowth
Language	English
Dates of publication	2022-0714
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms10071421
Database	NAL-Catalogue (AGRICOLA)

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Article: Moxifloxacin Activates the SOS Response in

Iacobino, Angelo / Piccaro, Giovanni / Pardini, Manuela / Fattorini, Lanfranco / Giannoni, Federico

Microorganisms

2021 Volume 9, Issue 2

Abstract: Previous studies ... ...

Abstract	Previous studies on
Language	English
Publishing date	2021-01-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms9020255
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Article: Activity of Drug Combinations against

Lanni, Alessio / Borroni, Emanuele / Iacobino, Angelo / Russo, Cristina / Gentile, Leonarda / Fattorini, Lanfranco / Giannoni, Federico

Microorganisms

2022 Volume 10, Issue 7

Abstract	Infections caused by Mycobacterium abscessus (Mab), an environmental non-tuberculous mycobacterium, are difficult to eradicate from patients with pulmonary diseases such as cystic fibrosis and bronchiectasis even after years of antibiotic treatments. In these people, the low oxygen pressure in mucus and biofilm may restrict Mab growth from actively replicating aerobic (A) to non-replicating hypoxic (H) stages, which are known to be extremely drug-tolerant. After the exposure of Mab A and H cells to drugs, killing was monitored by measuring colony-forming units (CFU) and regrowth in liquid medium (MGIT 960) of 1-day-old A cells (A1) and 5-day-old H cells (H5). Mab killing was defined as a lack of regrowth of drug-exposed cells in MGIT tubes after >50 days of incubation. Out of 18 drugs tested, 14-day treatments with bedaquiline-amikacin (BDQ-AMK)-containing three-drug combinations were very active against A1 + H5 cells. However, drug-tolerant cells (persisters) were not killed, as shown by CFU curves with typical bimodal trends. Instead, 56-day treatments with the nitrocompounds containing combinations BDQ-AMK-rifabutin-clarithromycin-nimorazole and BDQ-AMK-rifabutin-clarithromycin-metronidazole-colistin killed all A1 + H5 Mab cells in 42 and 56 days, respectively, as shown by lack of regrowth in agar and MGIT medium. Overall, these data indicated that Mab persisters may be killed by appropriate drug combinations.
Language	English
Publishing date	2022-07-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms10071421
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Article ; Online: Novel Putative Transposable Element Associated with the Subtype E5 Botulinum Toxin Gene Cluster of Neurotoxigenic

Li, Tao / Ning, Nianzhi / Iacobino, Angelo / Zhang, Liangyan / Wang, Hui / Franciosa, Giovanna

International journal of molecular sciences

2022 Volume 23, Issue 2

Abstract: Previously, a whole-genome comparison of ... ...

Abstract	Previously, a whole-genome comparison of three
MeSH term(s)	Botulinum Toxins/genetics ; China ; Clostridium Infections/microbiology ; Clostridium butyricum/classification ; Clostridium butyricum/genetics ; Clostridium butyricum/isolation & purification ; Computational Biology ; DNA Transposable Elements ; Gene Rearrangement ; Genome, Bacterial ; Genomics/methods ; Humans ; Multigene Family ; Neurotoxins/genetics ; Phylogeny
Chemical Substances	DNA Transposable Elements ; Neurotoxins ; Botulinum Toxins (EC 3.4.24.69) ; botulinum toxin type E (T579M564JY)
Language	English
Publishing date	2022-01-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23020906
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Article: Moxifloxacin Activates the SOS Response in Mycobacterium tuberculosis in a Dose- and Time-Dependent Manner

Iacobino, Angelo / Piccaro, Giovanni / Pardini, Manuela / Fattorini, Lanfranco / Giannoni, Federico

Microorganisms. 2021 Jan. 27, v. 9, no. 2

2021

Abstract: Previous studies on Escherichia coli demonstrated that sub-minimum inhibitory concentration (MIC) of fluoroquinolones induced the SOS response, increasing drug tolerance. We characterized the transcriptional response to moxifloxacin in Mycobacterium ... ...

Abstract	Previous studies on Escherichia coli demonstrated that sub-minimum inhibitory concentration (MIC) of fluoroquinolones induced the SOS response, increasing drug tolerance. We characterized the transcriptional response to moxifloxacin in Mycobacterium tuberculosis. Reference strain H37Rv was treated with moxifloxacin and gene expression studied by qRT-PCR. Five SOS regulon genes, recA, lexA, dnaE2, Rv3074 and Rv3776, were induced in a dose- and time-dependent manner. A range of moxifloxacin concentrations induced recA, with a peak observed at 2 × MIC (0.25 μg/mL) after 16 h. Another seven SOS responses and three DNA repair genes were significantly induced by moxifloxacin. Induction of recA by moxifloxacin was higher in log-phase than in early- and stationary-phase cells, and absent in dormant bacilli. Furthermore, in an H37Rv fluoroquinolone-resistant mutant carrying the D94G mutation in the gyrA gene, the SOS response was induced at drug concentrations higher than the mutant MIC value. The 2 × MIC of moxifloxacin determined no significant changes in gene expression in a panel of 32 genes, except for up-regulation of the relK toxin and of Rv3290c and Rv2517c, two persistence-related genes. Overall, our data show that activation of the SOS response by moxifloxacin, a likely link to increased mutation rate and persister formation, is time, dose, physiological state and, possibly, MIC dependent.
Keywords	DNA repair ; Escherichia coli ; Mycobacterium tuberculosis ; drug resistance ; drugs ; gene expression ; moxifloxacin ; mutants ; mutation ; mutation rate ; physiological state ; regulon ; toxins ; transcription (genetics)
Language	English
Dates of publication	2021-0127
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms9020255
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Article: Activity of DNA-targeted C8-linked pyrrolobenzodiazepine-heterocyclic polyamide conjugates against aerobically and hypoxically grown Mycobacterium tuberculosis under acidic and neutral conditions.

Iacobino, Angelo / Giannoni, Federico / Fattorini, Lanfranco / Brucoli, Federico

The Journal of antibiotics

2018 Volume 71, Issue 9, Page(s) 831–834

Abstract: Mycobacterium tuberculosis (Mtb) is the aetiological agent of tuberculosis, the leading cause of death worldwide from a single infectious agent. Mtb is a highly adaptable human pathogen that might enter a dormant non-replicating (NR), drug-tolerant stage. ...

Abstract	Mycobacterium tuberculosis (Mtb) is the aetiological agent of tuberculosis, the leading cause of death worldwide from a single infectious agent. Mtb is a highly adaptable human pathogen that might enter a dormant non-replicating (NR), drug-tolerant stage. Reactivation of dormant Mtb can lead to active disease. Antibiotic treatments of active and latent tuberculosis are long, complex and may fail to fully eradicate the infection. Therefore, it is imperative to identify novel compounds with new mechanisms of action active against NR bacilli. Dormant Mtb habitat is mostly thought to be the pH-neutral and hypoxic caseous granuloma. We have used the Wayne culture model to reproduce this environment and tested the activities of two DNA-targeted agents, C8-linked-pyrrolobenzodiazepine(PBD)-polyamide conjugates 1 and 2, against Mtb grown in aerobic and hypoxic conditions in both acidic and pH-neutral media. PBD 2 showed growth inhibitory activity at 5.1 µg/ml against 19-day-old hypoxic NR Mtb cultures with 1.8 log
MeSH term(s)	Anaerobiosis ; Antitubercular Agents/pharmacology ; Benzodiazepines/chemistry ; Benzodiazepines/pharmacology ; Cell Line ; Humans ; Isoniazid/pharmacology ; Mycobacterium tuberculosis/drug effects ; Mycobacterium tuberculosis/growth & development ; Nylons/chemistry ; Nylons/pharmacology ; Pyrroles/chemistry ; Pyrroles/pharmacology ; Rifampin/pharmacology ; Tuberculosis, Pulmonary/drug therapy
Chemical Substances	Antitubercular Agents ; Nylons ; Pyrroles ; pyrrolo(2,1-c)(1,4)benzodiazepine ; Benzodiazepines (12794-10-4) ; Isoniazid (V83O1VOZ8L) ; Rifampin (VJT6J7R4TR)
Language	English
Publishing date	2018-05-24
Publishing country	Japan
Document type	Journal Article
ZDB-ID	390800-8
ISSN	1881-1469 ; 0021-8820 ; 0368-3532
ISSN (online)	1881-1469
ISSN	0021-8820 ; 0368-3532
DOI	10.1038/s41429-018-0068-5
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Zs.A 207: Show issues

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ab Jg. 2022: Lesesaal (EG)

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Article ; Online: The Combination Rifampin-Nitazoxanide, but Not Rifampin-Isoniazid-Pyrazinamide-Ethambutol, Kills Dormant Mycobacterium tuberculosis in Hypoxia at Neutral pH.

Iacobino, Angelo / Giannoni, Federico / Pardini, Manuela / Piccaro, Giovanni / Fattorini, Lanfranco

Antimicrobial agents and chemotherapy

2019 Volume 63, Issue 7

Abstract: The activities of rifampin, nitazoxanide, PA-824, and sutezolid were tested against ... ...

Abstract	The activities of rifampin, nitazoxanide, PA-824, and sutezolid were tested against dormant
MeSH term(s)	Antitubercular Agents/pharmacology ; Drug Combinations ; Drug Therapy, Combination ; Ethambutol/pharmacology ; Humans ; Hydrogen-Ion Concentration ; Hypoxia ; Isoniazid/pharmacology ; Microbial Sensitivity Tests ; Mycobacterium tuberculosis/drug effects ; Nitroimidazoles/pharmacology ; Oxazolidinones/pharmacology ; Pyrazinamide/pharmacology ; Rifampin/pharmacology ; Tuberculosis/microbiology
Chemical Substances	Antitubercular Agents ; Drug Combinations ; Nitroimidazoles ; Oxazolidinones ; PNU-100480 ; isoniazid, pyrazinamide, rifampin drug combination ; pretomanid ; Pyrazinamide (2KNI5N06TI) ; Ethambutol (8G167061QZ) ; Isoniazid (V83O1VOZ8L) ; Rifampin (VJT6J7R4TR)
Language	English
Publishing date	2019-06-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	217602-6
ISSN	1098-6596 ; 0066-4804
ISSN (online)	1098-6596
ISSN	0066-4804
DOI	10.1128/AAC.00273-19
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Zs.A 809: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Einzelsignatur: Show issues

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Article ; Online: Galleria mellonella as an in vivo model for assessing the protective activity of probiotics against gastrointestinal bacterial pathogens.

Scalfaro, Concetta / Iacobino, Angelo / Nardis, Chiara / Franciosa, Giovanna

FEMS microbiology letters

2017 Volume 364, Issue 7

Abstract: The antagonistic activity against gastrointestinal bacterial pathogens is an important property of probiotic bacteria and a desirable feature for pre-selection of novel strains with probiotic potential. Pre-screening of candidate probiotics for ... ...

Abstract	The antagonistic activity against gastrointestinal bacterial pathogens is an important property of probiotic bacteria and a desirable feature for pre-selection of novel strains with probiotic potential. Pre-screening of candidate probiotics for antibacterial activity should be based on in vitro and in vivo tests. This study investigated whether the protective activity of probiotic bacteria against gastrointestinal bacterial pathogens can be evaluated using Galleria mellonella larvae as an in vivo model. Larvae were pre-inoculated with either of two widely used probiotic bacteria, Lactobacillus rhamnosus GG or Clostridium butyricum Miyairi 588, and then challenged with Salmonella enterica Typhimurium, enteropathogenic Escherichia coli or Listeria monocytogenes. Survival rates increased in the probiotic pretreated larvae compared with control larvae inoculated with pathogens only. The hemocyte density increased as well in the probiotic pretreated larvae, indicating that both probiotics induce an immune response in the larvae. The antibacterial activity of probiotics against the pathogens was also assayed by an in vitro agar spot test: results were partially consistent with those obtained by the G. mellonella protection assay. The results obtained, as a whole, suggest that G. mellonella larvae are a potentially useful in vivo model that can complement in vitro assays for pre-screening of candidate probiotics.
MeSH term(s)	Animals ; Antibiosis ; Bacterial Adhesion ; Clostridium butyricum/physiology ; Culture Media ; Enteropathogenic Escherichia coli/pathogenicity ; Enteropathogenic Escherichia coli/physiology ; Gastrointestinal Tract/microbiology ; Hemocytes/physiology ; Lactobacillus rhamnosus/physiology ; Larva/microbiology ; Listeria monocytogenes/physiology ; Models, Animal ; Moths/microbiology ; Probiotics ; Salmonella typhimurium/physiology
Chemical Substances	Culture Media
Language	English
Publishing date	2017-04-01
Publishing country	England
Document type	Journal Article
ZDB-ID	752343-9
ISSN	1574-6968 ; 0378-1097
ISSN (online)	1574-6968
ISSN	0378-1097
DOI	10.1093/femsle/fnx064
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