Major issues
The phrase “drug resistance in host” is also unclear. It needs to be revised so as to reflect the paper’s actual focus.
The manuscript mainly discusses immune modulation, persistence, and LAM as a biomarker, rather than explaining how LAM contributes to antimicrobial drug resistance.
The objective and scope are not clearly stated. The claim that LAM is linked to “drug resistance” needs to be supported and distinguished from immune evasion and bacterial persistence.
Section 1, The section contains extensive background on TB pathogenesis, but does not clearly identify the knowledge gap or explain how the paper is organized to address it. Some statements about granulomas, MDR-TB, and bacterial persistence are broad and need more precise qualification.
Section 2, “LAM and Antimicrobial Response”: This section combines immune evasion, oxidative stress, phagosome maturation, diagnostic testing, and treatment monitoring without a clear progression.
The authors should distinguish host immune evasion from antimicrobial drug resistance and explain the relevance of each subsection to the central topic.
Section 3, “LAM as Yardstick…”: The claim that LAM indicates bacterial identity, burden, virulence, treatment response, and prognosis is too broad. The authors should distinguish established diagnostic or prognostic evidence from proposed applications, and clarify the populations and settings in which the cited findings apply.
The suggestion that LAM can help manage latent or MDR-TB and serve as a target for host-directed therapy is not sufficiently developed in the preceding discussion. These should be presented as potential research directions, not established applications.
Overall structure and evidence should be more critically looked into, acknowledge conflicting evidence, and identify key knowledge gaps.
Minor issues
Throughout, authors should standardize capitalization and terminology, including “drug resistance,” “Mycobacterium tuberculosis,” “M. tuberculosis,” “ManLAM,” and “PI-LAM.”
Figure 1's caption is repeated, and several abbreviations should be checked for accuracy and defined consistently.
References: Author should correct the duplicated numbering in reference 2, the incomplete publication year in reference 20, and the duplicated reference entries (references 9 and 11). As well, check all in-text citations against the reference list.
Authors should break up long, information-dense sentences and define abbreviations at first use.
In addition, there are some grammatical issues within the paper e.g "predisposing patient asymptomatic". Authors should review such issues.
Competing interests
The authors declare that they have no competing interests.
Use of Artificial Intelligence (AI)
The authors declare that they did not use generative AI to come up with new ideas for their review.