Cysteamine/Cystamine Exert Anti-Mycobacterium abscessus Activity Alone or in Combination with Amikacin
Host-directed therapies are emerging as a promising tool in the curing of difficult-to-treat infections, such as those caused by drug-resistant bacteria. In this study, we aim to test the potential activity of the FDA- and EMA-approved drugs cysteamine and cystamine against Mycobacterium abscessus. In human macrophages (differentiated THP-1 cells), these drugs restricted M. abscessus growth similar to that achieved by amikacin. Here, we use the human ex vivo granuloma-like structures (GLS) model of infection with the M. abscessus rough (MAB-R) and smooth (MAB-S) variants to study the activity of new therapies against M. abscessus. We demonstrate that cysteamine and cystamine show a decrease in the number of total GLSs per well in the MAB-S and MAB-R infected human peripheral blood mononuclear cells (PBMCs). Furthermore, combined administration of cysteamine or cystamine with amikacin resulted in enhanced activity against the two M. abscessus morpho variants compared to treatment with amikacin only. Treatment with cysteamine and cystamine was more effective in reducing GLS size and bacterial load during MAB-S infection compared with MAB-R infection. Moreover, treatment with these two drugs drastically quenched the exuberant proinflammatory response triggered by the MAB-R variant. These findings showing the activity of cysteamine and cystamine against the R and S M. abscessus morphotypes support the use of these drugs as novel host-directed therapies against M. abscessus infections.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:24 |
|---|---|
| Enthalten in: |
International journal of molecular sciences - 24(2023), 2 vom: 07. Jan. |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Palucci, Ivana [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
5UX2SD1KE2 |
|---|
| Anmerkungen: |
Date Completed 24.01.2023 Date Revised 01.02.2023 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.3390/ijms24021203 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM351854371 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM351854371 | ||
| 003 | DE-627 | ||
| 005 | 20231226052403.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3390/ijms24021203 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1172.xml |
| 035 | |a (DE-627)NLM351854371 | ||
| 035 | |a (NLM)36674717 | ||
| 035 | |a (PII)1203 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Palucci, Ivana |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Cysteamine/Cystamine Exert Anti-Mycobacterium abscessus Activity Alone or in Combination with Amikacin |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 24.01.2023 | ||
| 500 | |a Date Revised 01.02.2023 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Host-directed therapies are emerging as a promising tool in the curing of difficult-to-treat infections, such as those caused by drug-resistant bacteria. In this study, we aim to test the potential activity of the FDA- and EMA-approved drugs cysteamine and cystamine against Mycobacterium abscessus. In human macrophages (differentiated THP-1 cells), these drugs restricted M. abscessus growth similar to that achieved by amikacin. Here, we use the human ex vivo granuloma-like structures (GLS) model of infection with the M. abscessus rough (MAB-R) and smooth (MAB-S) variants to study the activity of new therapies against M. abscessus. We demonstrate that cysteamine and cystamine show a decrease in the number of total GLSs per well in the MAB-S and MAB-R infected human peripheral blood mononuclear cells (PBMCs). Furthermore, combined administration of cysteamine or cystamine with amikacin resulted in enhanced activity against the two M. abscessus morpho variants compared to treatment with amikacin only. Treatment with cysteamine and cystamine was more effective in reducing GLS size and bacterial load during MAB-S infection compared with MAB-R infection. Moreover, treatment with these two drugs drastically quenched the exuberant proinflammatory response triggered by the MAB-R variant. These findings showing the activity of cysteamine and cystamine against the R and S M. abscessus morphotypes support the use of these drugs as novel host-directed therapies against M. abscessus infections | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Mycobacterium abscessus | |
| 650 | 4 | |a cystamine | |
| 650 | 4 | |a cysteamine | |
| 650 | 4 | |a host-directed therapies | |
| 650 | 4 | |a transglutaminase-2 | |
| 650 | 7 | |a Amikacin |2 NLM | |
| 650 | 7 | |a 84319SGC3C |2 NLM | |
| 650 | 7 | |a Anti-Bacterial Agents |2 NLM | |
| 650 | 7 | |a Cysteamine |2 NLM | |
| 650 | 7 | |a 5UX2SD1KE2 |2 NLM | |
| 650 | 7 | |a Cystamine |2 NLM | |
| 650 | 7 | |a R110LV8L02 |2 NLM | |
| 700 | 1 | |a Salustri, Alessandro |e verfasserin |4 aut | |
| 700 | 1 | |a De Maio, Flavio |e verfasserin |4 aut | |
| 700 | 1 | |a Pereyra Boza, Maria Del Carmen |e verfasserin |4 aut | |
| 700 | 1 | |a Paglione, Francesco |e verfasserin |4 aut | |
| 700 | 1 | |a Sali, Michela |e verfasserin |4 aut | |
| 700 | 1 | |a Occhigrossi, Luca |e verfasserin |4 aut | |
| 700 | 1 | |a D'Eletto, Manuela |e verfasserin |4 aut | |
| 700 | 1 | |a Rossin, Federica |e verfasserin |4 aut | |
| 700 | 1 | |a Goletti, Delia |e verfasserin |4 aut | |
| 700 | 1 | |a Sanguinetti, Maurizio |e verfasserin |4 aut | |
| 700 | 1 | |a Piacentini, Mauro |e verfasserin |4 aut | |
| 700 | 1 | |a Delogu, Giovanni |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t International journal of molecular sciences |d 2008 |g 24(2023), 2 vom: 07. Jan. |w (DE-627)NLM185552161 |x 1422-0067 |7 nnns |
| 773 | 1 | 8 | |g volume:24 |g year:2023 |g number:2 |g day:07 |g month:01 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.3390/ijms24021203 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 24 |j 2023 |e 2 |b 07 |c 01 | ||