CHAPTER

Microorganisms and antibiotic

production

Kanwal Rehman1, Sania Niaz1, 2, Ayesha Tahir1,2, Muhammad Sajid Hamid Akash3
1
1
Department of Pharmacy, University of Agriculture, Faisalabad, Pakistan; 2Institute of Physiology and Pharmacology,
University of Agriculture, Faisalabad, Pakistan; 3Department of Pharmaceutical Chemistry, Government College
University Faisalabad, Faisalabad, Pakistan

1.1 Introduction
Microorganisms are organisms or infectious agents of microscopic or submicroscopic size, which
include bacteria, fungi, protozoans, and viruses. For the treatment of infections, antimicrobial drugs
are valuable due to selectivity of their toxicity, thereby having capability to kill the invading micro-
organisms without harming the host cells. Antimicrobial medicines can be classified according to their
action against the microorganisms. For example, antibiotics are used against bacteria, whereas anti-
fungals are specifically used against fungi. The term probiotic was introduced by Lilly and Stillwell
(Lilly and Stillwell, 1965).

1.2 Probiotics
The use of probiotics for their health benefits is increasing worldwide (Agheyisi, 2005). The word
probiotic is derived from the Greek word meaning for life and has had several different meanings over
the years. Improving the host health by consumption of live microorganisms provides a basic concept of
a probiotic. A probiotic can be defined as microorganism introduced into the body in sufficient quantity
for its beneficial qualities into the host. Gut health or microflora can be improved by the utilization of
typical microorganisms that are present in fermented products (Hill et al., 2014; Ndowa et al., 2012).
According to the mechanistic approach, disorder or imbalance of important intestinal microflora leads to
many gastrointestinal infirmity or infections. Probiotics are viable microbial cultures that maintain or
balance the microflora of intestine, correct the microbial dysfunction, and enhance the host health and
well-being (Fuller, 1989; Rokka and Rantamäki, 2010). Two of the most common microbes that are
widely used as probiotics are Lactobacillus and Bifidobacteria strains. Growth of the concerned
microorganism is stimulated by using the bacterial culture of probiotics, which improves the natural
defensive mechanism of the body and also disrupts the harmful bacteria (Dunne, 2001).
Probiotics have shown a curative role against cancer, and they also have been shown to reduce
cholesterol levels, modify lactose intolerance, and enhance immunity (Kailasapathy and Chin, 2000).
As probiotics boost immunity, they provide beneficial health effects by the stimulation of cell-
Antibiotics and Antimicrobial Resistance Genes in the Environment. https://doi.org/10.1016/B978-0-12-818882-8.00001-2
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2 Chapter 1 Microorganisms and antibiotic production

mediated immune responses as well as enhance the antibody secretions. Probiotics are selected ac-
cording to the protection point of view against microbial pathogens (Cross, 2002) and also play a vital
role in maintaining the overweight of an obese adult (Kadooka et al., 2010).

1.3 Prebiotics
Prebiotic concepts were introduced in 1995 by Gibson and Roberfroid as a substitute approach to alter or
modify the microbiota of the gut (Gibson and Roberfroid, 1995). A prebiotic is a nondigestible food
ingredient, usually bifidobacteria and lactobacilli, that beneficially affects the host by enhancing the
growth and/or activity of one or a limited number of specific species of bacteria in the gut, thus
strengthening the host health. They are indigestible by human enzymes because they have short-chain
carbohydrates (SCCs), so-called resistant SCCs (Quigley et al., 1999). To be considered as a prebiotic,
a food ingredient must have specific properties. For example, (1) it should be resistant by passing the
upper portion of gastrointestinal track for the absorption and hydrolysis; (2) it should provide a favorable
environment by modifying the microflora of the colon and provide more healthy and favorable compo-
sition there; and (3) it should show specific property of selective substrate for one or a specific amount of
colon bacteria (Park and Kroll, 1993). Hence there are numerous potential applications of prebiotics.
Prebiotics should be resistant to being hydrolyzed by intestinal enzymes of the human but should
be fermented by specific bacteria and should have fruitful effects for the host. Upon administration,
prebiotics should have beneficial outcomes including lowering the permeability of intestine,
decreasing triglyceride levels, and improving glucose levels after eating (Cani et al., 2009; Gibson and
Roberfroid, 1995). Prebiotics are widely used as a supplement and can be formulated in various ways
such as syrups or powder and also into different food products, particularly in bread and yogurt, that
provide beneficial health effects by enhancing the minerals’ bioavailability (Roberfroid et al., 2010).
They have also been recommended for improved bone and mineral metabolism.

1.4 Symbiotics
It has been suggested that symbiotics are the combination of probiotics and prebiotics, not only
comprising the combined effects of these two probiotics and prebiotics but also purposed to have a
synergistic effect (Rafter et al., 2007).

1.5 Antibiotics
Many of the antibiotics are the essential excretions of environmental bacteria and fungi. At present,
these antibiotics are used as a major source of human medicines for the treatment of infections (Kieser
et al., 2000).

1.5.1 Classification of antibiotics

The most important classification of antibiotics is based on their spectrum, mode of action, and mo-
lecular structure. There are certain ways to classify antibiotics (Calderón and Sabundayo, 2007),
notably, one method is based on their route of administration such as topically, orally, or as an
 1.7 Production of antibiotics 3

injectable. Other antibiotics that are related to the same structural class will show analogous patterning
of efficiency, allergic side effects, and toxicity. Some common classes of antibiotics like macrolides,
quinolones, tetracyclines, aminoglycosides, sulfonamides, oxazolidinones, glycopeptides, and beta-
lactam are based on their molecular and chemical structures (Adzitey, 2015; Frank and Tacconelli,
2012; Van Hoek et al., 2011). For many years, antibiotics have proven efficacious in providing a
curative response for many contagious diseases. Antibiotics include composites that hinder the growth
of microorganisms, which are considered as “antimicrobial agents.” Several natural antibiotics can
also be used in the treatment of numerous diseases.

1.5.2 Mechanisms of antibiotic resistance

Antibiotic resistance came into existence between 1940 and 1970. There are several ways for the
development of antibiotic resistance that are described in the following subsections.

1.5.3 Enzymatic inactivation

In enzymatic inactivation, the primitive enzyme undergoes modification by reacting with the antibiotic
and then the antibiotic cannot kill the microorganism. The most common example is b-lactamase
enzymes which causes hydrolysis of antibiotics and ultimately leads to antibiotic resistance against
penicillins and cephalosporins.

1.5.4 Drug elimination

In Pseudomonas aeruginosa and Acinetobacter species, the most important resistance mechanism is
drug elimination due to the excitation of efflux pump. Bacteria activate the proteins that cause the
removal of compounds from periplasm to outside of the cell to remove the antibiotics.

1.5.5 Permeability changes

Due to the alterations in outer membrane portability, there is a decrease in uptake of administered
antibiotics, due to which the adequate access to the antibiotics is blocked.

1.6 Modifications of antimicrobial targets

Three different types of antibiotic adjuvants have been invented that can be used to block the antibiotic
resistance mechanisms. These may include the (1) inhibitors of b-lactamases, (2) inhibitors of efflux
pump, and (3) permeabilization of outer membrane (Clatworthy et al., 2007; Rasko and Sperandio,
2010). The World Health Organization has recommended an antimicrobial resistance control policy
that includes increased supervision, development of new molecules, and rational use of antibiotics.

1.7 Production of antibiotics

Most antibiotics are produced by staged fermentations in which strains of microorganisms producing
high yields are grown under optimum conditions. It is important that the organism that is used for the
4 Chapter 1 Microorganisms and antibiotic production

production of antibiotic must be identified and isolated. The microorganism must be grown enough for
the purification and chemical analysis of the isolated antibiotics. Sterile conditions must be followed
during the purification and isolation of antibiotics because contamination by foreign microbes may
ruin the fermentation of the antibiotics. Following are the most commonly used techniques for the
production of antibiotics.

1.7.1 Natural production of antibiotics

In natural production, fermentation technique is used for the production of antibiotics. The most
common example of an antibiotic produced by this method is penicillin.

1.7.2 Semisynthetic production of antibiotics

This method is used for the production of natural antibiotics, for example, ampicillin.

1.7.3 Synthetic production of antibiotics

This method is used for the production of antibiotics in a laboratory. For example, the production of
quinoline is done by this method.

1.7.4 Industrial production of antibiotics

In this technique, the source microorganism is grown in large containers containing a liquid growth
medium. In this technique, the oxygen concentration, temperature, pH, and nutrient levels must be
optimum. As the antibiotics are secondary metabolites, their production must be controlled to ensure
that the maximum yield of antibiotics is obtained before the cells die.

1.7.5 Methods for increased production of antibiotics

Species for the production of specific antibiotics are often genetically modified to yield the maximum
amounts of antibiotics. Mutations and gene amplification techniques are used to increase the pro-
duction of antibiotics.

1.8 Stability of antimicrobial agents

According to several research studies, many kinds of encapsulation procedures and materials are used
for microencapsulation and coating of antibiotics (Hébrard et al., 2010; Nag et al., 2011; Papagianni
and Anastasiadou, 2009). To preserve the antibiotics from the unpleasant conditions in the intestinal
tract, microencapsulation technique is widely used (Anal and Singh, 2007; Kailasapathy, 2002).
Microencapsulation technique plays an important role by separating the core material from
environmental conditions until it gets released, thereby modifying stability and viability and
improving shelf life and helping to provide the controlled and sustained release of encapsulated
products. The outer structure is formed by microencapsulation technique around the core. This
property provides a core with characteristics of controlled-release product under favorable
 References 5

environmental conditions and also provides a way for small molecules to pass out of and into the
membrane. At the time of release of encapsulated core material at the favorable site, it follows
different mechanistic approaches including dissolution of the cell wall, melting of the cell wall,
diffusion through the wall, and breakage of the cell wall (F. Gibbs, 1999; Franjione and Vasishtha,
1995).

1.9 Conclusion
For the better efficacy of antimicrobial agents against microorganisms, efficient methods should be
chosen for the production and purification of antimicrobial agents. As the stability of antimicrobial
agents is a major concern, it is mandatory that appropriate technique should be adopted for the
encapsulation of antimicrobial agents.

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