# Halophytes as Medicinal Plants against Human Infectious Diseases
## 4 Current Limitations and Future Prospects  
There is a generalized consensus around the potential of plant metabolites as novel antimicrobials or coadjutants for antimicrobial chemotherapy. Being well represented in costal and arid regions, haplotypes have been long used in traditional medicine and are, therefore, immediate candidates for the screening of new bioactive metabolites. There are, in fact, several studies that establish the link between the empiric use of these plants to treat infections with the photochemistry evidence of the compounds that underlie antimicrobial effects. However, efforts in the investigation of new antimicrobial compounds and the demonstration of their effect in vitro have not yet resulted in an antibiotic sufficiently effective to be clinically advantageous and economically profitable. The concern around drug-resistant microbes has drawn attention to plant-derived, effective antimicrobial compounds. A new life is waiting for plants that have been used for centuries in infectious disease treatment. The detection and quantification of known, and even the discovery of new, small bioactive molecules produced by plants as secondary metabolites will provide new forms of therapy for numerous infectious and noninfectious illnesses. Appropriate and optimized extraction methods, susceptibility tests and clinical trials are still required. The prospects of the outcomes of further investigations seem promising and may lead to significant advances with the potential discovery of new and effective treatments [115; 116]. Mass-spectrometry-based plant metabolomics is an extremely powerful approach, likely to provide comprehensive metabolite profiles of medicinal haplotypes in the near future. In vitro tests represent the first approach to screen promising metabolites, either purified or as mixtures, for antimicrobial effects. The complexity and diverse chemical properties of plant metabolites demands a combined use of analytical platforms to increase the detection coverage of these compounds in biological samples. To detect volatile and nonvolatile metabolites, it is essential to use GC and HPLC coupled with mass spectrometry, as well as other techniques such as UPLC or NMR to ensure that all or at least the majority of compounds are separated, detected, identified, quantified and characterized. Each method should also cover several extraction solvents to ensure the detection of both polar and nonpolar compounds. The isolation and chemical characterization of each compound, by NMR technologies and testing them in bioassays, is crucial to move towards the assessment of the biological activity of each compound. The methodological approaches for in vitro tests must, however, be carefully adjusted to the chemical nature of the metabolites or extracts. Protocols need to be standardized and validated against representative biological models so that comparisons between products are reliable and meaningful. Many bioactive metabolites are expressed by plants in response to stress or induced by environmental conditions or microbial symbionts colonizing plant tissues [117]. Examples of the most characteristic biologically active metabolites found in haplotypes are the phenolic acids, sterols and terpenoids, among others (Figure 4). The targeted manipulation on the plant microbiome is, therefore, regarded as a strategy to modulate the metabolome and to induce the expression of high added-value metabolites, such as antimicrobial compounds. Considering that the root is an important gateway for bacteria that are able to establish stable, mutually beneficial relations with the plant hosts (plant-growth-promoting bacteria), the modification of the rhizosphere microbiome with selected inoculants (rhizosphere engineering) represents an all-new line of research towards the general objective of plant-derived, effective antimicrobial compounds. **Author Contributions:** Conceptualization, D.C.G.A.P., A.C. and H.S.