An optimized cyclophosphamide-treated mouse model of <i>Mycobacterium abscessus</i> pulmonary infection

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

ABSTRACT

Mycobacterium abscessus pulmonary infections are increasingly problematic, especially for immunocompromised individuals and those with underlying lung conditions. Currently, there is no reliable standardized treatment, underscoring the need for improved preclinical drug testing. We present a simplified immunosuppressed mouse model using only four injections of cyclophosphamide, which allows for sustained M. abscessus lung burden for up to 16 days. This model proved effective for antibiotic efficacy evaluation, as demonstrated with imipenem or amikacin.

Related collections

Most cited references 21

Record: found
Abstract: not found
Article: not found

Epidemiology of infection by nontuberculous mycobacteria.

J Falkinham (1996)

0 comments Cited 162 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

Is Open Access

The Role of Antibiotic-Target-Modifying and Antibiotic-Modifying Enzymes in Mycobacterium abscessus Drug Resistance

Sakshi Luthra, Anna Rominski, Peter Sander (2018)

The incidence and prevalence of non-tuberculous mycobacterial (NTM) infections have been increasing worldwide and lately led to an emerging public health problem. Among rapidly growing NTM, Mycobacterium abscessus is the most pathogenic and drug resistant opportunistic germ, responsible for disease manifestations ranging from “curable” skin infections to only “manageable” pulmonary disease. Challenges in M. abscessus treatment stem from the bacteria’s high-level innate resistance and comprise long, costly and non-standardized administration of antimicrobial agents, poor treatment outcomes often related to adverse effects and drug toxicities, and high relapse rates. Drug resistance in M. abscessus is conferred by an assortment of mechanisms. Clinically acquired drug resistance is normally conferred by mutations in the target genes. Intrinsic resistance is attributed to low permeability of M. abscessus cell envelope as well as to (multi)drug export systems. However, expression of numerous enzymes by M. abscessus, which can modify either the drug-target or the drug itself, is the key factor for the pathogen’s phenomenal resistance to most classes of antibiotics used for treatment of other moderate to severe infectious diseases, like macrolides, aminoglycosides, rifamycins, β-lactams and tetracyclines. In 2009, when M. abscessus genome sequence became available, several research groups worldwide started studying M. abscessus antibiotic resistance mechanisms. At first, lack of tools for M. abscessus genetic manipulation severely delayed research endeavors. Nevertheless, the last 5 years, significant progress has been made towards the development of conditional expression and homologous recombination systems for M. abscessus. As a result of recent research efforts, an erythromycin ribosome methyltransferase, two aminoglycoside acetyltransferases, an aminoglycoside phosphotransferase, a rifamycin ADP-ribosyltransferase, a β-lactamase and a monooxygenase were identified to frame the complex and multifaceted intrinsic resistome of M. abscessus, which clearly contributes to complications in treatment of this highly resistant pathogen. Better knowledge of the underlying mechanisms of drug resistance in M. abscessus could improve selection of more effective chemotherapeutic regimen and promote development of novel antimicrobials which can overwhelm the existing resistance mechanisms. This article reviews the currently elucidated molecular mechanisms of antibiotic resistance in M. abscessus, with a focus on its drug-target-modifying and drug-modifying enzymes.

0 comments Cited 98 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Clinical and microbiologic outcomes in patients receiving treatment for Mycobacterium abscessus pulmonary disease.

Lening Zhang, G. Huitt, Lisa A. Levin … (2011)

Mycobacterium abscessus can produce a chronic pulmonary infection for which little is known regarding optimal treatment and long-term outcomes. We performed a retrospective observational study (2001-2008) including all patients who met American Thoracic Society criteria for M. abscessus pulmonary disease. Our aim was the evaluation of clinical and microbiologic outcomes in patients treated with combined antibiotic and surgical therapy, compared with antibiotic therapy alone. A total of 107 patients were included in the analysis. Patients were predominantly female (83%) and never-smokers (60%), with a mean age of 60 years. Fifty-nine (55%) of 107 patients had coexistent or previous history of Mycobacterium avium complex pulmonary infection. High-resolution chest CT showed bronchiectasis and nodular opacities in 98% of patients and cavities in 44%. Sixty-nine (46 medical, 23 surgical) patients were followed up for a mean duration of 34 months (standard deviation, 21.1 months, range, 2-82 months). Cough, sputum production, and fatigue remained stable, improved, or resolved in 80%, 69%, and 59% of patients, respectively. Twenty (29%) of 69 patients remained culture positive, 16 (23%) converted but experienced relapse, 33 (48%) converted to negative and did not experience relapse, and 17 (16%) died during the study period. There were significantly more surgical patients than medical patients whose culture converted and remained negative for at least 1 year (57% vs 28%; P = .022). Patients with M. abscessus pulmonary disease who are treated with multidrug antibiotic therapy and surgery or antibiotic therapy alone had similar clinical outcomes. However, surgical resection, in addition to antibiotics, may offer a prolonged microbiologic response.

0 comments Cited 74 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Sung Jae Shin: (View ORCID Profile)

Kevin Pethe: (View ORCID Profile)

Journal

Title: Antimicrobial Agents and Chemotherapy

Abbreviated Title: Antimicrob Agents Chemother

Publisher: American Society for Microbiology

ISSN (Print): 0066-4804

ISSN (Electronic): 1098-6596

Publication date Created: August 07 2024

Publication date (Print): August 07 2024

Volume: 68

Issue: 8

Affiliations

[1 ]Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore

[2 ]Antimicrobial Resistance Interdisciplinary Research Group, Singapore-MIT Alliance for Research and Technology Centre, Singapore, Singapore

[3 ]Interdisciplinary Graduate Programme, Nanyang Technological University, Singapore, Singapore

[4 ]Critical Analytics for Manufacturing of Personalized Medicine (CAMP) Interdisciplinary Research Group, Singapore-MIT Alliance for Research and Technology Centre, Singapore, Singapore

[5 ]Department of Microbiology, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, South Africa

[6 ]Chemical Engineering and Biotechnology, Nanyang Technological University, Singapore, Singapore

[7 ]Centre for Antimicrobial Bioengineering, Nanyang Technological University, Singapore, Singapore

[8 ]Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, Singapore, Singapore

[9 ]National Centre for Infectious Diseases, Singapore, Singapore

Article

DOI: 10.1128/aac.01520-23

SO-VID: 6522ef4d-54f3-45c7-bcb6-c767e5f47081

License:

https://doi.org/10.1128/ASMCopyrightv2

https://journals.asm.org/non-commercial-tdm-license

History

Data availability:

Comments

Comment on this article

scite_

Smart Citations

Citing PublicationsSupportingMentioningContrasting

View Citations

See how this article has been cited at scite.ai

scite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.