**4.2 Period 1991–2000**

For the period 1991–2000, the retrieval yielded 23,470 documents from PubMed. The top 10 clusters that emerged from the co-word analysis are presented in the form of a strategic diagram in **Figure 3**. The corresponding summary of the identified research topics is given in **Table 2**.

In the observed period, the biggest cluster was the cluster "Gene Expression Regulation, Bacterial/drug effects" comprised of the MeSH headings dealing with drug or radiation effects on the genes, their expression, and regulation. This cluster was found to be the basic theme in this time period. A typical representative article for this cluster is the article published by Lutz and Bujard with the title "Independent and tight regulation of transcriptional units in *Escherichia coli* via the LacR/O, the TetR/O and AraC/I1-I2 regulatory elements" [35].

#### **Figure 3.**

*Strategic diagram of the period 1991–2000. Each research topic is represented by a node and labeled with the most frequent pair MeSH heading/MeSH subheading. The size of the node is proportional to the number of MeSH heading/MeSH subheading pairs in each cluster.*

*Exploring the Knowledge Landscape of* Escherichia coli *Research: A Scientometric Overview DOI: http://dx.doi.org/10.5772/intechopen.109207*


#### **Table 2.**

*Principal research topics related to* E. coli *research in the period 1991–2000.*

A further important basic research time in this period was also encompassed in the cluster "*Escherichia coli*/genetics" including the MeSH headings relating also to *E. coli* metabolism and enzymology, and growth and development. A typical representative article for this cluster is the article published by Hiraga with the title "Chromosome partition in *Escherichia coli*" [36]. The major motor theme in this period was covered by the cluster "*Escherichia coli*/immunology" involving also MeSH related to epidemiology, diagnosis, pathogenesis, and drug therapy of *E. coli* infections. A typical representative article for this cluster is the article published by Johnson with the title "Virulence factors in *Escherichia coli* urinary tract infection" [37]. The major niche theme was the cluster "Bacterial Toxins/chemistry", covering different MeSH headings dealing with genetics, chemistry, metabolism, and toxicity of bacterial toxins and enterotoxins. A typical representative article for this cluster is the article published by Gyles with the title "*Escherichia coli* cytotoxins and enterotoxins" [38].

#### **4.3 Period 2001–2010**

For the period 2001–2010, the search strategy retrieved 24,266 documents. Selected research topics are shown in **Figure 4** (here we point out to the reader that we have included the 11 most important research topics, while the ranks of clusters 7–9 are tied). The contextual meaning of the clusters is summarized in **Table 3**.

#### **Figure 4.**

*Strategic diagram of the period 2001–2010. Each research topic is represented by a node and labeled with the most frequent pair MeSH heading/MeSH subheading. The size of the node is proportional to the number of MeSH heading/MeSH subheading pairs in each cluster.*

In the period 2001–2010, the biggest cluster was the cluster "*Escherichia coli*/ genetics" comprised of very diverse MeSH headings dealing with genetics and classification, but also with enzymology, metabolism and drug effects, isolation, purification and chemistry, cytology, growth, and development and also pathogenicity. This cluster was found to be the only basic theme in this time period. A typical representative article for this cluster is the article published by Tenaillon et al. with the title "The population genetics of commensal *Escherichia coli*" [39].

The major motor theme in this period was covered by the cluster "*Escherichia coli* Proteins/metabolism" involving MeSH headings related to metabolism and isolation and purification of different native, but also recombinant bacterial proteins. A typical representative article for this cluster is the article published by Bell with the title "Structure and mechanism of *Escherichia coli* RecA ATPase" [40]. Among motor themes, another cluster of very similar size was revealed—the cluster "*Escherichia coli* Infections/microbiology" covering the MeSH heading relating to important *E. coli* infection topics associated with pathogenic *E. coli*, e.g., urinary tract infections and bacteremia, but also antimicrobial agents with special emphasis on the topic of beta-lactamases. A typical representative article for this cluster is the article published by Croxen and Finlay with the title "Molecular mechanisms of *Escherichia coli* pathogenicity" [41]. In this time period no niche themes were found.

*Exploring the Knowledge Landscape of* Escherichia coli *Research: A Scientometric Overview DOI: http://dx.doi.org/10.5772/intechopen.109207*


**Table 3.**

*Principal research topics related to* E. coli *research in the period 2001–2010.*

#### **4.4 Period 2011–2021**

In the last observed period, we analyzed 30,114 bibliographic records from PubMed. The co-word analysis revealed six thematic clusters, as shown in **Figure 5**. The corresponding details are presented in **Table 4**.

In the period 2011–2022 was again the biggest cluster the cluster "*Escherichia coli*/genetics" comprised of very diverse MeSH headings dealing with genetics and genetically modified microorganisms, but also with enzymology, metabolism, biosynthesis, purification and chemistry, and growth and development. This cluster was again the basic theme in this time period. A typical representative article for this cluster is the article published by Yang et al. with the title "*Escherichia coli* as a platform microbial host for systems metabolic engineering" [42]. A further important basic research time in this period was also encompassed in the cluster "*Escherichia coli*/drug effects" consisting of the MeSH headings relating to bacterial drug resistance. A typical representative article for this cluster is the article published by Da Silva and Mendonça with the title "Association between antimicrobial resistance and virulence in *Escherichia coli*" [43]. Only one major motor theme in this period was revealed, covered by the cluster "Anti-Bacterial Agents/ pharmacology" covering MeSH headings related to different aspects, e.g., pharmacology, chemistry of antibacterial agents, including silver and antimicrobial cationic

#### **Figure 5.**

*Strategic diagram of the period 2011–2021. Each research topic is represented by a node and labeled with the most frequent pair MeSH heading/MeSH subheading. The size of the node is proportional to the number of MeSH heading/MeSH subheading pairs in each cluster.*


*Exploring the Knowledge Landscape of* Escherichia coli *Research: A Scientometric Overview DOI: http://dx.doi.org/10.5772/intechopen.109207*


**Table 4.**

*Principal research topics related to* E. coli *research in the period 2011–2021.*

peptides. A typical representative article for this cluster is the article published by Zhao et al. with the title "Synthesis of Ag/AgCl modified anhydrous basic bismuth nitrate from BiOCl and the antibacterial activity" [44]. The major niche theme in this period was covered by the cluster "Recombinant Fusion Proteins/genetics" wrapping the topics of genetics, biosynthesis, chemistry, and isolation and purification of recombinant fusion proteins. A typical representative article for this cluster is the article published by Jeffery with the title "Expression, solubilization, and purification of bacterial membrane proteins" [45]. The second cluster among the niche themes in this time period is the cluster "Recombinant Proteins/genetics" covering the topics of genetics, metabolism, and chemistry of recombinant proteins. A typical representative article for this cluster is the article published by Gopal and Kumar with the title "Strategies for the production of recombinant protein in *Escherichia coli*" [46].

### **5. Discussion**

*E. coli* is known to be a versatile microorganism—it is a commensal in the gut microbiota of healthy hosts, but can be found also as a pathogen instigating intestinal but also extraintestinal infections [47]. *E. coli* is also a well-known probiotic bacterium, as some important probiotic drugs including *E. coli* are on the market [48–50]. Further, it is a very well-known model microorganism for Gram-negative bacteria, which was and still is used as a laboratory "workhorse" on which many basic topics of molecular biology, physiology, genetics, evolution, genetic engineering, and biotechnology were and still are studied [51–53].

So there is no surprise in finding many papers published on *E. coli*. Bibliometric co-word analysis has the potential to reveal the topic trends in *E. coli* research. The result of this kind of analysis is two-dimensional plots in which circles (i.e., nodes), whose size corresponds to the number of including MeSH terms, are partitioned into different quadrants. The top right quadrant depicts motor themes with strong centrality as well as high density. The upper left quadrant shows specialized themes, which refer to themes having a high density, but also having inadequate external interactions. The bottom-right quadrant shows the basic themes—these are themes that have a strong centrality, but low density. In the bottom, left quadrant themes are shown that are emerging or declining, as they have in general low density and centrality. For just one strategic diagram, it is usually not possible to determine whether a theme is emerging or declining, however, when data from several graphs, each from a certain period, are compared, for some themes that are found in more graphs a trend can be established. From our analysis, it can be assumed that the cluster "Anti-Bacterial Agents/pharmacology" which appeared in the 1981–1990 period in the quadrant of Emerging or declining themes was in that time period an emerging theme, as the same cluster can be also found in the graphs of the periods 2001–2010 and 2011–2022, namely in the quadrant of motor themes. A similar can

be stated for the cluster "Plasmids/genetics", which appeared on the strategic diagram of the period 1991–2000 was an emerging theme, as the same cluster can be found also in the 2001–2010 diagram, namely in the quadrant of motor themes. An example of a declining cluster theme is the cluster "Gene Expression Regulation, Bacterial/drug effects" which is the major basic theme in the diagram of the time period 1991–2000, but moved to the emerging or declining themes quadrant in the plot of the time period 2001–2010. In the strategic diagram of the period 2011–2021 in the emerging or declining themes quadrant the cluster "Microfluidic Analytical Techniques/instrumentation" appeared, which is for sure an emerging cluster as much of the *E. coli* research is now moving into the area of single cell analysis which is enabled by the microfluidic techniques.
